No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Free Radicals in the Genesis of Alzheimer's Diseasea
Abstract
As part of an ongoing investigation of the role of oxygen free radicals in Alzheimer's disease (AD), the formation of peroxidation products, the activities of free radical defense enzymes, and the level of total iron were determined in autopsy brain tissue from donors with AD and from age-matched non-demented donors. Calcium uptake was also investigated in mitochondria harvested from fibroblasts grown in tissue culture from skin samples taken from brain donors.
Compared to controls, homogenates of AD frontal cortex produced elevated levels of peroxidation products and this difference was amplified in a dose-dependent manner by iron (1 to 200 μM). Peroxidation produced by 200 μM iron was reduced dose dependently by the lazaroid U-74500A. The IC50 was 10 μM in AD cortex and 2.5 μM in controls.
Superoxide dismutase (SOD), one of the free radical defensive enzymes, was reduced by 25 to 35% in AD frontal cortex, hippocampus and cerebellum. In other brain areas, SOD did not differ between AD and control. The activities of catalase and glutathione peroxidase were the same in AD and control samples. Endogenous iron levels were higher in AD frontal cortex (2.5 nmol/mg protein) than in controls (1.5 nmol/mg protein).
Calcium uptake by AD fibroblast mitochondria is 50% lower than in controls under basal conditions. Following exposure to 200 μM iron, mitochondrial calcium uptake is increased by 58% in AD and by 38% in controls. Pretreatment with 200 μM U-74500A or 1 mM deferoxamine, prior to exposure to 200 μM iron, gave complete protection to control mitochondria but gave only partial protection to AD mitochondria.
These studies indicate that in AD, both CNS and peripheral cells show increased sensitivity to oxygen free radicals. The source of this increased sensitivity has not yet been identified but could reflect either reduced free radical defenses or increased free radical formation or both. Work is underway using electron paramagnetic resonance spectrometry to determine in vivo, premortem free radical activity in AD patients.
... All these alterations were largely confirmed in mitochondria of cultured neurons and forebrain samples of several PD mouse models (Mortiboys et al., 2008;Grunewald et al., 2010;Pacelli et al., 2011;Van Der Merwe et al., 2014;Lopez-Fabuel et al., 2017). In the case of AD, several studies had shown that fibroblasts of patients with FAD presented a reduction in the mitochondrial number and respiratory function (Gray and Quinn, 2015), high levels of ROS (Richardson, 1993;Moreira et al., 2007), reduced levels of antioxidant defenses (Cecchi et al., 2002), and mitochondrial calcium handling defects (Richardson, 1993;Ito et al., 1994); Therefore, our results presented here indicate that fibroblasts obtained from SAD patients could also present the mitochondrial dysfunction features observed in the AD brain. ...
... All these alterations were largely confirmed in mitochondria of cultured neurons and forebrain samples of several PD mouse models (Mortiboys et al., 2008;Grunewald et al., 2010;Pacelli et al., 2011;Van Der Merwe et al., 2014;Lopez-Fabuel et al., 2017). In the case of AD, several studies had shown that fibroblasts of patients with FAD presented a reduction in the mitochondrial number and respiratory function (Gray and Quinn, 2015), high levels of ROS (Richardson, 1993;Moreira et al., 2007), reduced levels of antioxidant defenses (Cecchi et al., 2002), and mitochondrial calcium handling defects (Richardson, 1993;Ito et al., 1994); Therefore, our results presented here indicate that fibroblasts obtained from SAD patients could also present the mitochondrial dysfunction features observed in the AD brain. ...
The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients.
... In the fight against numerous illnesses (such as cancer, chronic inflammation, atherosclerosis, and cardiovascular disorders), antioxidants are regarded as important molecules. 55 Phlorotannins, a type of polyphenol found in marine brown algae, are recognised as possible antioxidants. Phloroglucinol (1,3,5trihydroxybenzene) monomer units are polymerized to form phlorotannins, which are produced by marine algae using the acetate-malonate pathway. ...
The marine is the primary source of uniquely structured natural materials, which are primarily found in living things. Marine algae have long been utilised as food and medicine and are crucial to the ecology. Marine creatures have the potential to be abundant sources of highly bioactive secondary metabolites that could serve as valuable starting points for the creation of novel pharmaceuticals. The sea is regarded as the largest remaining pool of natural molecules to be assessed for therapeutic activity and provides a tremendous resource for novel compounds due to the fact that marine animals make up around half of all species in the world. It is a real fact that the importance of marine organisms as a source of new substances is growing. Algae can be divided into two primary categories: macroalgae (seaweeds), which includes green, brown, and red algae, and microalgae, which includes blue-green algae, dinoflagellates, bacillariophyta (diatoms), etc. The natural bioactive compounds found in marine algae have been demonstrated to be a rich source of anti-diabetic, anti-inflammatory, antiviral, antifungal, hypolipidemic, antioxidant, anti-hypercholesterolemia, antibacterial, and antineoplastic activities. They generate fresh secondary metabolites with potential for use as pharmaceuticals because of their biological activity. The potential pharmacological, therapeutic, and research applications of these substances have been covered in this review.
... Previous studies linked the relationship between the rate of ROS destruction and the ability of the body to remove ROS, which happened as a consequence of oxidative damage that induces tissue injury [13,14]. Previously reported studies revealed the significance of several important brain areas known to exhibit cognitive effects and require antioxidants as essential nutritional supplements [15]. Previous data demonstrated that the neurodegeneration process might also include inflammation of neurons, an increase in ROS, which results in oxidative damage, and biochemical alterations in the brain that ultimately cause neuronal death [16]. ...
Materials and methods:
Oral acute toxicity studies were performed to evaluate the toxicological effects of europinidin in animals. In this study, four different animal groups (n = 6) were used. Group I was the normal control, group II was the STZ-induced diabetes control, group III was STZ + europinidin-treated (10 mg/kg), and group IV was STZ + europinidin-treated (10 mg/kg). The efficacy of europinidin at a dose of 10 mg/kg and 20 mg/kg was studied with single-dose administration of streptozotocin, which experimentally induced memory impairments in Wistar male rats for 38 days. The mean body weight and blood glucose levels were recorded at the initial and end of the study. The two behavioural paradigms (Y-maze and Morris water maze) were performed to evaluate spatial and working memory in rats. The biochemical parameters such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, and nitric oxide level as hallmarks of oxidative stress were measured. Additionally, the proinflammatory parameters were also determined to evaluate the neuroinflammatory responses associated with streptozotocin such as tumor necrosis factor-alpha (TNF-α) interleukin-1β (IL-1β), interleukin (IL-6), nuclear factor-kappa B (NF-ƙB), interleukin (IL-10), and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in the perfused brain.
Results:
The rats in the europinidin-treated group exhibited a significant restoration of body weight and blood glucose level as compared with the streptozotocin control group. Furthermore, europinidin significantly modulated the spatial and working memory in rats, when assessed through behavioural paradigms. Streptozotocin caused a significant alteration in biochemical, neuronal enzymatic, and neuroinflammatory parameters, which were significantly restored to normal levels by europinidin.
Conclusion:
The present study attributed the neuroprotective efficacy of europinidin in experimental animal models by subsiding the several biomarkers of oxidative stress, neuroinflammation, and neuronal enzymatic activities.
... Azalan serbest radikal veya artan serbest radikal oluşumunda denge bozulmaktadır. AD hastalarında in vivo, premortem serbest radikal aktivitesini belirlemek için elektron paramanyetik rezonans spektrometresi kullanılarak çalışmalar devam etmektedir (Richardson, 1993) (Hensley vd., 1994). ...
HEMODİYALİZ HASTALARINDA YORGUNLUĞU AZALTMAK İÇİN KULLANILAN TAMAMLAYICI TERAPİLER
... Oxidative damage of brain tissue has been widely acknowledged to play a role in learning and memory impairment in animals, especially the prefrontal cortex and hippocampus, which are very sensitive to oxidative stress [104,105]. Memory and learning are impaired by the increased production of free radicals and oxidative stress in brain tissue [106,107]. High body adiposity may induce the production of ROS, promoting chronic inflammation [108], and fatty acids are involved in catabolism through peroxisomal β-oxidative and mitochondrial pathways [109]. ...
Prolonged daily intake of Western-type diet rich in saturated fats and sugars, and exposure to early life stress have been independently linked to impaired neurodevelopment and behaviour in animal models. However, sex-specific effects of both environmental factors combined on spatial learning and memory, behavioural flexibility, and brain oxidative capacity have still not been addressed. The current study aimed to evaluate the impact of maternal and postnatal exposure to a high-fat and high-sugar diet (HFS), and exposure to early life stress by maternal separation in adult male and female Wistar rats. For this purpose, spatial learning and memory and behavioural flexibility were evaluated in the Morris water maze, and regional brain oxidative capacity and oxidative stress levels were measured in the hippocampus and medial prefrontal cortex. Spatial memory, regional brain oxidative metabolism, and levels of oxidative stress differed between females and males, suggesting sexual dimorphism in the effects of a HFS diet and early life stress. Males fed the HFS diet performed better than all other experimental groups independently of early life stress exposure. However, behavioural flexibility evaluated in the spatial reversal leaning task was impaired in males fed the HFS diet. In addition, exposure to maternal separation or the HFS diet increased the metabolic capacity of the prefrontal cortex and dorsal hippocampus in males and females. Levels of oxidative stress measured in the latter brain regions were also increased in groups fed the HFS diet, but maternal separation seemed to dampen regional brain oxidative stress levels. Therefore, these results suggest a compensatory effect resulting from the interaction between prolonged exposure to a HFS diet and early life stress.
... Moreover, oxidative stress was demonstrated to disturb learning and memory. 25 In our study, the increased level of MDA but decreased levels of CAT, SOD, and total thiols were found after LPS injection in the brain of LPS group as compared to the control group. Similar to our results, it has also been previously reported that LPS injection is followed by an imbalance in oxidant-anti oxidant system in both the hippocampus and cortex. ...
The study was aimed to evaluate the effects of hydro-ethanol extract Zataria multiflora on the brain tissue oxidative damage, and hippocampal interleukin-6 (IL-6) as well as learning and memory capacity in lipopolysaccharide (LPS) - challenged rats. The rats were randomized into five groups as follow: Control group: Rats were treated with saline, LPS group: Rats were treated with LPS 1.00 mg kg-1, ZM50, ZM100 and ZM200 groups in which the rats were treated with Z. multiflora extract (50.00, 100 or 200 mg kg-1 per day, respectively). The treatments including extract or vehicle were administered intraperitoneally and given three days before the behavioral tests and were continued within a6-day behavioral experiment. Injection of LPS was daily done before the behavioral tests. Finally, the brains were collected for biochemical evaluations. Although LPS administration prolonged the latency in Morris water maze and shortened the latency to enter the dark chamber in passive avoidance test, ZM extract restored these changes to approach control group values. Also, LPS increased IL-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites levels and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) levels in the brain, however, Z. multiflora extract reduced IL-6, MDA and NO metabolites concentrations, but increased thiol content, SOD, and CAT levels. The results of this study showed that Z. multiflora ameliorated learning and memory dysfunction in LPS - challenged rats by alleviating of inflammatory responses and brain tissue oxidative damage.
... The activity of catalase was found reduced in the basal ganglia, amygdala, and parietal-temporal cortex in the AD brain (Gsell et al., 1995). Reduction of SOD activity in the frontal cortex, hippocampus, and cerebellum in AD has also been reported (Richardson, 1993). There have also been reports of diminished SOD activity in the caudate nucleus (Marklund et al., 1985), and reduction in SOD activity in the frontal and temporal lobes; and reduction in catalase activity in the temporal cortex (Marcus et al., 1998). ...
... It is suggested that the level of vitamin C decreases in the brain of the cognitively impaired and AD individuals [271]. It has been reported that the AD patients are characterized by increased level and activity of ROS [272] due to the deposition of Aβ [273], activation of microglia cells [274], neuronal mitochondrial dysfunctioning [275], disturbance in the redox metal metabolic pathway [63,64,276], and the deficiencies of neurotransmitters such as noradrenaline and serotonin [277]. Further, the observation from the studies suggested that the CSF:plasma ratio of vitamin C rises significantly in the AD patients compared to the controls, suggesting the increased consumption of antioxidants by the brain in AD patients [278]. ...
Alzheimer’s disease (AD) is considered the sixth leading cause of death in elderly patients and is characterized by progressive neuronal degeneration and impairment in memory, language, etc. AD is characterized by the deposition of senile plaque, accumulation of fibrils, and neurofibrillary tangles (NFTs) which are responsible for neuronal degeneration. Amyloid-β (Aβ) plays a key role in the process of neuronal degeneration in the case of AD. It has been reported that Aβ is responsible for the production of reactive oxygen species (ROS), depletion of endogenous antioxidants, increase in intracellular Ca2+ which further increases mitochondria dysfunctions, oxidative stress, release of pro-apoptotic factors, neuronal apoptosis, etc. Thus, oxidative stress plays a key role in the pathogenesis of AD. Antioxidants are compounds that have the ability to counteract the oxidative damage conferred by ROS. Therefore, the antioxidant therapy may provide benefits and halt the progress of AD to advance stages by counteracting neuronal degeneration. However, despite the beneficial effects imposed by the antioxidants, the findings from the clinical studies suggested inconsistent results which might be due to poor study design, selection of the wrong antioxidant, inability of the molecule to cross the blood–brain barrier (BBB), treatment in the advanced state of disease, etc. The present review insights into the neuroprotective effects and limitations of the antioxidant therapy for the treatment of AD by targeting mitochondrial-derived ROS. This particular article will certainly help the researchers to search new avenues for the treatment of AD by utilizing mitochondrial-derived ROS-targeted antioxidant therapies.
... It is suggested that the level of vitamin C decreases in the brain of the cognitively impaired and AD individuals [271]. It has been reported that the AD patients are characterized by increased level and activity of ROS [272] due to the deposition of Aβ [273], activation of microglia cells [274], neuronal mitochondrial dysfunctioning [275], disturbance in the redox metal metabolic pathway [63,64,276], and the deficiencies of neurotransmitters such as noradrenaline and serotonin [277]. Further, the observation from the studies suggested that the CSF:plasma ratio of vitamin C rises significantly in the AD patients compared to the controls, suggesting the increased consumption of antioxidants by the brain in AD patients [278]. ...
Alzheimer’s disease (AD) is considered the sixth leading cause of death in elderly patients and is characterized by progressive neuronal degeneration and impairment in memory, language, etc. AD is characterized by the deposition of senile plaque, accumulation of fibrils, and neurofibrillary tangles (NFTs) which are responsible for neuronal degeneration. Amyloid-β (Aβ) plays a key role in the process of neuronal degeneration in the case of AD. It has been reported that Aβ is responsible for the production of reactive oxygen species (ROS), depletion of endogenous antioxidants, increase in intracellular Ca²⁺ which further increases mitochondria dysfunctions, oxidative stress, release of pro-apoptotic factors, neuronal apoptosis, etc. Thus, oxidative stress plays a key role in the pathogenesis of AD. Antioxidants are compounds that have the ability to counteract the oxidative damage conferred by ROS. Therefore, the antioxidant therapy may provide benefits and halt the progress of AD to advance stages by counteracting neuronal degeneration. However, despite the beneficial effects imposed by the antioxidants, the findings from the clinical studies suggested inconsistent results which might be due to poor study design, selection of the wrong antioxidant, inability of the molecule to cross the blood–brain barrier (BBB), treatment in the advanced state of disease, etc. The present review insights into the neuroprotective effects and limitations of the antioxidant therapy for the treatment of AD by targeting mitochondrial-derived ROS. This particular article will certainly help the researchers to search new avenues for the treatment of AD by utilizing mitochondrial-derived ROS-targeted antioxidant therapies.
Graphical abstract
... Under situations where a rise in ROS generation is present, these lipids can be peroxidated, which will ultimately affect the activity of complex IV [115]. Accordingly, decreased activity of complex IV and increased lipid peroxidation has been found in various samples, including brains obtained from patients of AD [116][117][118]. At the same time, this affection of complex IV increases the generation of superoxide by complexes I-III [119]. ...
Alzheimer’s Disease (AD) is the most common neurodegenerative disorder in our society, as the population ages, its incidence is expected to increase in the coming decades. The etiopathology of this disease still remains largely unclear, probably because of the highly complex and multifactorial nature of AD. However, the presence of mitochondrial dysfunction has been broadly described in AD neurons and other cellular populations within the brain, in a wide variety of models and organisms, including post-mortem humans. Mitochondria are complex organelles that play a crucial role in a wide range of cellular processes, including bioenergetics. In fact, in mammals, including humans, the main source of cellular ATP is the oxidative phosphorylation (OXPHOS), a process that occurs in the mitochondrial electron transfer chain (ETC). The last enzyme of the ETC, and therefore the ulterior generator of ATP, is the ATP synthase. Interestingly, in mammalian cells, the ATP synthase can also degrade ATP under certain conditions (ATPase), which further illustrates the crucial role of this enzyme in the regulation of cellular bioenergetics and metabolism. In this collaborative review, we aim to summarize the knowledge of the presence of dysregulated ATP synthase, and of other components of mammalian mitochondrial bioenergetics, as an early event in AD. This dysregulation can act as a trigger of the dysfunction of the organelle, which is a clear component in the etiopathology of AD. Consequently, the pharmacological modulation of the ATP synthase could be a potential strategy to prevent mitochondrial dysfunction in AD.
... Polyphenols, phycobiliprotein, and vitamin are important water-soluble antioxidants in algae, antioxidants able to cause degeneration premalignant lesions and inhibit their progress into cancer. Algae prohibited oxygen damage by hunting free radicals and active oxygen and, therefore, the incidence of cancer will be avoided (Richardson, 1993). These antioxidants can be used against various diseases, like cardiovascular disorder, chronic inflammation, and atherosclerosis (Kohen and Nyska, 2002). ...
Natural biodiversity of plants faces different abiotic problems, most noticeable are drought, salinity, and metals toxicity. Physiological and biological functions of various plant biodiversity are harshly affected by different metal (Ni, Cd, Pb) stress. Different areas of Punjab are metal-polluted due to various activities, like unsatisfactory irrigation system, industrial pollution, etc. It is hypothesized that plants grown in such habitats are able to tolerate metal contamination. Ecologically different areas of Punjab that are metal and salt polluted are under study and different 2ecotypes of Typhadomingensis Pers. have been collected from such areas. The ecotypes from these metals polluted and saline areas were exposed to metal (nickel) stress to assess their degree of tolerance and adaptive response under measured environmental conditions. Four levels of nickel were maintained (0, 50, 100, and 150 mg kg−1) in the growth medium. Different data were recorded for morpho-anatomical, physiological, and biochemical characteristics. The treatments were placed in a completely randomized design (CRD) with six replications.
... Brain tissue oxidative damage has also been well known to have a role learning and memory impairments in LPS animal model (Pourganji et al. 2014). Cortex and hippocampus, which play important roles in learning and memory, are very sensitive to oxidative stress (Richardson 1993). Increasing the production of free radicals and causing oxidative stress in brain tissue impair memory and learning and antioxidants improve this process (Papandreou et al. 2011). ...
Inflammation can cause memory impairment. In the present study, the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide (LPS)-challenged rats was evaluated. The animals were grouped and treated: (1) control which received vehicle instead of LPS and carvacrol, (2) LPS (1 mg/kg; i.p. 120 min before behavioral tests), and (3–5) in these groups, 25, 50, or 100 mg/kg of carvacrol (i.p.) was administered 30 min prior to LPS. In a Morris water maze test, compared to LPS group, administration of all three doses of carvacrol shortened the elapsed time and the traveled distance to find the platform, while it prolonged the traveled time in the target area. In a passive avoidance test, administration of all 25, 50, and 100 mg/kg carvacrol significantly increased the latency at the 3 h, 24 h, 48 h, and 72 h after the shock compared to the LPS group. Interleukin (IL)-6, malondialdehyde (MDA), and NO (nitric oxide) metabolites were increased in the brain by LPS injection, while thiol, superoxide dismutase (SOD), and catalase (CAT) were decreased. Pretreatment with carvacrol reduced IL-6, NO metabolites, and MDA, while it improved thiol content, CAT, and SOD. The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress in LPS-challenged rats.
... Free radicals have oxygen free radicals and hydroxyl radicals. SOD is an important antioxidant enzyme in the body and it can remove free radicals and prevent the free radical chain reaction initiated by O2 (Manczak et al. 2006;Richardson 2010). In addition, the newly formed unsaturated fatty acid radical is combined with the unsaturated fatty acid of another molecule to produce a n ew m o l e cu l e of l i p i d f re e r ad i c al , w h i ch i s decomposed into MDA (Gustaw-Rothenberg et al. 2010). ...
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases which seriously affect the quality of life of the elderly. Schisandrin (SCH) and nootkatone (NKT) are the two marked active components in ASHP. In this study, the effects of Alpinia oxyphylla—Schisandra chinensis herb pair (ASHP) as well as its bioactive components on cognitive deficiency and dementia were revealed via Aβ1–42-induced AD in mouse. Morris water maze test showed that acute administration of ASHP and SCH + NKT treatments had higher discrimination index in the object recognition task, more quadrant dwell time and shorter escape latency compared with those in the Morris water maze. The levels of TNF-α, IL-1β and IL-6 were decreased after ASHP and SCH + NKT treatment. The inflammatory response was attenuated by inhibiting TLR4/ NF-κB/ NLRP3 pathway. In addition, ASHP and SCH + NKT treatments significantly restored the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), cyclooxygenase-2 (COX-2), total antioxidant capacity (T-AOC) and inducible nitric oxide syntheses (iNOS), and the levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO). The histopathological changes of hippocampus were noticeably improved after ASHP and SCH + NKT treatments. These findings demonstrate that ASHP as well as its bioactive components exerted a protective effects on cognitive disorder, inflammatory reaction and oxidative stress.
... Seaweeds have good antioxidant properties, which play a major role to fight against various diseases like cancer, chronic inflammation, atherosclerosis and cardiovascular disorder and ageing processes [48]. It also prevents the rate of cancer cell formation [50]. ...
Seaweed research has been carried out for more than seven decades by many research workers. Research has been done separately in different aspects accordingly to our need. The main objective of the present review is to gather information relating to nutritional, pharmacological, clinical, biochemical, industrial uses and its application to human welfare. Seaweeds have a high concentration of essential vitamins, trace elements, proteins, lipids, polysaccharides, enzymes, and minerals as compared to terrestrial foodstuffs. These plants have been a source of food, fodder, medicine, cosmetics, energy, fertilizer and are used for industrial production of agar and alginate. Their recent utilization increases in poultry due to their nutritive value. In the present scenario, it is being used for wastewater treatment such as treatment of wastewater to reduce nitrogen and phosphorus containing compounds. This review work is an attempt to highlights all the relevant application and uses of seaweeds and its products. Finally, this paper would be helpful to a common man to know and aware about such a great living resources which is present in and around us.
... Polyphenols, phycobiliprotein, and vitamin are important water-soluble antioxidants in algae, antioxidants able to cause degeneration premalignant lesions and inhibit their progress into cancer. Algae prohibited oxygen damage by hunting free radicals and active oxygen and, therefore, the incidence of cancer will be avoided (Richardson, 1993). These antioxidants can be used against various diseases, like cardiovascular disorder, chronic inflammation, and atherosclerosis (Kohen and Nyska, 2002). ...
Algae are a diverse group that are used in medicine from long times. They
produce secondary metabolites, such as proteins, vitamins, fatty acids,
pigments, and polysaccharides, which have a pharmaceutical value and
play an important role in medicine. Such biologically active products
(bromophenols, sulfated polysaccharides, c-phycocyanin, phycobilipro-
tein, ß-carotene, peptides, etc.) can be used as antioxidants, anticancer,
antimicrobial (antibacterial, antifungal), anti-inflammatory, anticoagulant,
immune enhancer and modulator, antidiabetic, reduction of fats, cosmetic, and thalassotherapy. And this is not restricted on marine algae or macroalgae but even microalgae and cyanobacteria can produce pharmaceutical and nutraceutical value products. This study concludes that algae are natural future drugs.
... The results of studies on the activity of SOD in people with AD are ambiguous. There are reports showing a decrease in SOD activity within the frontal cortex and a slight increase in activity in the caudate nucleus in AD patients, as well as a lack of changes in the activity of this enzyme in AD patients [61][62][63]. Increased activity of the mitochondrial SOD isoform (SOD2) has been reported in the hippocampus of people diagnosed with AD [64,65]. An increase in SOD2 activity has been observed in the area that is usually the most degenerated, i.e. ...
It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.
... 73 In agreement, levels of expression/activity of antioxidant enzymes, such as Cu/Zn-and Mn-superoxide dismutase (SOD), were reported to be decreased in AD brains compared to control subjects. [74][75][76] Interestingly, a compensatory increase in the expression of Mn-SOD and glutathione reductase (GSSG-R) proteins was described in MCI. 77 Even in AD patients, protein and mRNA levels of glutathione peroxidase, GSSG-R and catalase were increased, compared to control subjects, in selective areas also characterized by increased lipid peroxidation. ...
Alzheimer's disease (AD) is characterized by extensive neurodegeneration and inflammation in selective brain areas, linked to severely disabling cognitive deficits. Before full manifestation, different stages appear with progressively increased brain pathology and cognitive impairment. This significantly extends the time lag between initial molecular triggers and appearance of detectable symptoms. Notably, a number of studies in the last decade have revealed that in the early stage of mild cognitive impairment, events that appear in contrast with neuronal distress may occur. These have been reproduced in vitro and in animal models and include increase in synaptic elements, increase in synaptic and metabolic activity, enhancement of neurotrophic milieu and changes in glial cell reactivity and inflammation. They have been interpreted as compensatory responses that could either delay disease progression or, in the long run, result detrimental. For this reason, these mechanisms define a new and previously undervalued window of opportunity for intervention. Their importance resides especially in their early appearance. Directing efforts to better characterize this stage, in order to identify new pharmacological targets, is an exciting new avenue to future advances in AD research.
... The ROS together with, unstable intermediates in the peroxidation of lipid, are well known inducers of cellular and tissue pathogenesis leading to numerous disease states, including cardiovascular disease [3] and age-related degenerative condition [4,5]. Neurodegenerative disease, such as Alzheimer's disease [6], and cancer [7], are also linked to damage from ROS as a result of an imbalance between the rate of radical generation and their scavenging [8]. The primary formation of most of the ROS is the reduction of molecular oxygen with the formation of superoxide [9,10]. ...
... In, general, the generation and scavenging of oxygen free radicals is balanced and any imbalance or excessive amounts of active radicals may contribute to disease development. It has been found that free radical reactions can produce deleterious modifications in membranes, proteins, enzymes, and DNA [2], increasing the risk of diseases such as cancer [3], Alzheimer's [4], Parkinson's [5], angiocardiopathy [6], arthritis [7], asthma [8], diabetes [9] and degenerative eye disease [10]. ...
Objective: The objective of the present work deals with the synthesis, characterization and evaluation of antimicrobial and antioxidant activity of N-phenylpropyl-3-substituted indoline-2-one derivatives. Methods: A series of new 3-hydroxy-3-(2-oxoethyl)-1-(3-phenylpropyl) indolin-2-one derivatives 3(a-l) and 3-(2-oxoethylidene)-1-(3-phenylpropyl) indolin-2-one derivatives 4(a-l) were synthesized by knoevenagel condensation of N-phenylpropyl-5-substituted indole-2,3-diones with various acetophenones analogues. The chemical structures of synthesized compounds were confirmed by IR, 1 HNMR and Mass spectroscopic and elemental data. These compounds were also screened for their in vitro antimicrobial and antioxidant activities. Results: Novel compounds 3-hydroxy-3-(2-oxoethyl)-1-(3-phenylpropyl) indolin-2-one derivatives 3(a-l) and 3-(2-oxoethylidene)-1-(3-phenylpropyl) indolin-2-one derivatives 4(a-l) were synthesised and characterized using spectral and analytical data. The results of antibacterial and antifungal and antioxidant activities showed that some of the synthesized compounds exhibited promising results. Conclusion: All the newly synthesized compounds were screened for antimicrobial activity by cup plate method and antioxidant activity by the DPPH method using Ciprofloxacin and Amphotericin B as standards against gram positive and gram negative bacteria and fungi respectively.
... Vitamin C has been reported to be the first barrier to free radicals produced in biological fluids [102]. In the cognitively impaired, studies have demonstrated an increased sensitivity to free radicals in the cerebral cortex [103]. The mechanisms of free radical production hypothesized for AD include: activated microglia surrounding senile plaques [104], neuronal mitochondrial dysfunction [105], intraneuronal amyloid accumulation [106] and presence of redox active metals [107]. ...
Vitamin C plays a role in neuronal differentiation, maturation, myelin formation and modulation of the cholinergic, catecholinergic, and glutaminergic systems. This review evaluates the link between vitamin C status and cognitive performance, in both cognitively intact and impaired individuals. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library from 1980 to January 2017, finding 50 studies, with randomised controlled trials (RCTs, n = 5), prospective (n = 24), cross-sectional (n = 17) and case-control (n = 4) studies. Of these, 36 studies were conducted in healthy participants and 14 on cognitively impaired individuals (including Alzheimer’s and dementia). Vitamin C status was measured using food frequency questionnaires or plasma vitamin C. Cognition was assessed using a variety of tests, mostly the Mini-Mental-State-Examination (MMSE). In summary, studies demonstrated higher mean vitamin C concentrations in the cognitively intact groups of participants compared to cognitively impaired groups. No correlation between vitamin C concentrations and MMSE cognitive function was apparent in the cognitively impaired individuals. The MMSE was not suitable to detect a variance in cognition in the healthy group. Analysis of the studies that used a variety of cognitive assessments in the cognitively intact was beyond the scope of this review; however, qualitative assessment revealed a potential association between plasma vitamin C concentrations and cognition. Due to a number of limitations in these studies, further research is needed, utilizing plasma vitamin C concentrations and sensitive cognitive assessments that are suitable for cognitively intact adults.
... Polyphenols include a great range of molecular structures and they show important antioxidant activities in dietary plants (Rice et al. 1997;Paganga et al. 1999;Boyle et al. 2000;Kim et al. 2005): in fact, they protect human organism against cellular damage (Dimitrios 2006) and, accordingly, they prevent chronic diseases Hertog, Hollman 1996;Diplock et al. 1998;Lampe 1999). Notably, oxidation of DNA, proteins and lipids by reactive oxygen species (ROS) play an important role in aging and in a wide range of common diseases, including cancer and cardiovascular, inflammatory and neurodegenerative diseases, such as Alzheimer's, and other age-related degenerative conditions (Borek 1997;Richardson 1993). In fact, when in vitro cell cultures derived from animal (non-neoplastic) and human cell lines (neoplastic) are challenged with specific products, chemical markers or cytological changes are assessed such as oxidative DNA damage, apoptosis markers (such as DNA laddering) or increased production of free radical scavenging enzymes (Griffiths et al. 2002). ...
The aim of this review is a wide description of the relationships between growing conditions and bulb yield and quality of onion (Allium cepa L.), focused particularly on long-day cultivars suitable for storage. Marketable yield decreases according to the reduction of crop length caused by the increase of growth temperature. The nutritive requirements of storage onion are highest during the vegetative growth. The application of humic substances and the inoculation of mycorrhizae may enhance bulb growth and quality, mainly under stress conditions. Onion is a slow-growth, shallowrooted crop with non-shading habitus and therefore its productivity is highly dependent on water availability in the soil, proper fertilization and weed control. The shelf-life of onion bulbs is a genetic trait, improvable by efficient crop and post-harvest management, and adequate conditions of bulb storage. The quality of storage onion bulbs is ascribed to several indicators, such as thiosulfonates, pyruvic acid, soluble solids, sugars, and many other biological compounds. This review is also focused on onion quality as affected by the interactions among genotype, environment, farming practices and post-harvest management.
... Many authors describe elevated activity of SOD in distinct brain areas [65,66,67], which was also observed in our study, whereas others did not notice changes in enzyme activity in the brain [68,69]. Additionally, other studies describe a reduction of 25 to 35% in the activity of SOD in the cortex, hippocampus and cerebellum of AD patients [70]. ...
Alzheimer’s disease is a chronic and degenerative condition that had no treatment until recently. The current therapeutic strategies reduce progression of the disease but are expensive and commonly cause side effects that are uncomfortable for treated patients. Functional foods to prevent and/or treat many conditions, including neurodegenerative diseases, represent a promising field of study currently gaining attention. To this end, here we demonstrate the effects of pomegranate (Punica granatum) peel extract (PPE) regarding spatial memory, biomarkers of neuroplasticity, oxidative stress and inflammation in a mouse model of neurodegeneration. Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1–42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.– βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group. The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE. In conclusion, administration of pomegranate peel extract has neuroprotective effects involving multiple mechanisms to prevent establishment and progression of the neurodegenerative process induced by infusion with amyloid-β peptide in mice.
... The activity of catalase was found reduced in the basal ganglia, amygdala, and parietal-temporal cortex in the AD brain (Gsell et al., 1995). Reduction of SOD activity in the frontal cortex, hippocampus, and cerebellum in AD has also been reported (Richardson, 1993). There have also been reports of diminished SOD activity in the caudate nucleus (Marklund et al., 1985), and reduction in SOD activity in the frontal and temporal lobes; and reduction in catalase activity in the temporal cortex (Marcus et al., 1998). ...
Aβ pathology was produced in the rat brain by injecting aggregated Aβ40 or Aβ42 into the amygdala or hippocampus. Social behavior alterations in the rat with this pathology were studied by three-chamber social behavior test method. The data obtained show that sociability is impaired in rats in which the brain is afflicted with Aβ pathology, a condition similar to that in Alzheimer’s disease brain. It is to be noted that human-specific behaviors such as empathy, sympathy and pro-social behaviors exist in rodents, and in humans afflicted with Alzheimer’s disease social behaviors decline severely. The present study, thus, suggests that Aβ pathology/neurotoxicity may be involved in the genesis of social behavior changes.
... Seaweeds have good antioxidant properties, which play a major role to fight against various diseases like cancer, chronic inflammation, atherosclerosis and cardiovascular disorder and ageing processes [48]. It also prevents the rate of cancer cell formation [50]. ...
Seaweed research has been carried out for more than seven decades by many research workers. Research has been done separately in different aspects accordingly to our need. The main objective of the present review is to gather information relating to nutritional, pharmacological, clinical, biochemical, industrial uses and its application to human welfare. Seaweeds have a high concentration of essential vitamins, trace elements, proteins, lipids, polysaccharides, enzymes, and minerals as compared to terrestrial foodstuffs. These plants have been a source of food, fodder, medicine, cosmetics, energy, fertilizer and are used for industrial production of agar and alginate. Their recent utilization increases in poultry due to their nutritive value. In the present scenario, it is being used for wastewater treatment such as treatment of wastewater to reduce nitrogen and phosphorus containing compounds. This review work is an attempt to highlights all the relevant application and uses of seaweeds and its products. Finally, this paper would be helpful to a common man to know and aware about such a great living resources which is present in and around us.
Keywords: Seaweeds, Application, Human Welfare, Review
... Mitochondrial dysfunction and oxidative stress-induced damaging processes are regarded as major contributing factors being involved in learning and memory deficits related to the neurological disorders [41][42][43]. Compelling evidences have indicated that oxidative stress leads to mitochondrial dysfunction and subsequently, results in more ROS production and mitochondrial destabilization, which thereby causes neuronal death [44]. Furthermore, it is known that hippocampus and cerebral cortex are markedly susceptible to oxidative stress due to their high polyunsaturated lipid content, immense oxygen consumption, and low concentration of antioxidative enzymes [9,44]. ...
Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100 μg/kg/side) and H-89(10 μM) intra-hippocampally 30 min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders.
... Low antioxidant capacity and high oxygen consumption have made the brain tissues very susceptible to oxidative damage [1]. Cerebral cortex and hippocampus as the two crucial areas of memory formation, show the highest sensitivity to the oxidative stress [45]. Formerly in our laboratory, the role of the brain tissues oxidative damage in learning and memory impairment has also been confirmed [24,46,47]. ...
... GSE brought an increase in CAT and TAC. Considering SOD, Richardson [48] reported a decrease or reduction in SOD from 25% to 35% activity in AD frontal cortex, hippocampus and cerebellum. ...
... GSE brought an increase in CAT and TAC. Considering SOD, Richardson [48] reported a decrease or reduction in SOD from 25% to 35% activity in AD frontal cortex, hippocampus and cerebellum. ...
... The activity of catalase was found reduced in the basal ganglia, amygdala, and parietal-temporal cortex in the AD brain (Gsell et al., 1995). Reduction of SOD activity in the frontal cortex, hippocampus, and cerebellum in AD has also been reported (Richardson, 1993). There have also been reports of diminished SOD activity in the caudate nucleus (Marklund et al., 1985), and reduction in SOD activity in the frontal and temporal lobes; and reduction in catalase activity in the temporal cortex (Marcus et al., 1998). ...
Amyloid beta (Aβ) peptides are the principal constituents of senile plaques of Alzheimer's disease (AD) brain, and are thought to play an important role in the etiology and pathogenesis of AD. The present study assesses the responses of brain regions (hippocampus and amygdala) to amyloid toxicity in the light of behavioral and oxidative parameters. Aggregated Aβ 40 and Aβ-42 were stereotaxically injected into the hippocampus or amygdala, and their effects on cognitive (Morris water maze test) and non-cognitive (fear, anxiety, general emotional state: open field and light and dark chamber tests) behaviors were studied. Since human-specific social behaviors (empathy, sympathy etc.) also exist in rodents, the effect on these behaviors was also determined by three-chamber social behavior test. The oxidative stress generated by amyloid-β peptides is thought to contribute to the disease-associated behavioral deficits. Therefore, the present study also investigated the oxidative stress produced in the rat brain following amyloid injections. The oxidative stress produced by Aβ peptides was higher in the hippocampus compared with that in the amygdala. Similarly greater behavioral anomalies were caused in animals with intrahippocampal administration than in those with intraamygdalar administration. Thus, hippocampus showed a higher vulnerability to amyloid toxicity than amygdala. Furthermore, the results demonstrated that the oxidative stress spread from the injected site to distant brain regions like cortex, midbrain, cerebellum, and medulla. The results also showed that compared with Aβ 40 , Aβ 42 generated higher levels of oxidative stress and produced more severe behavioral deficits.. Copy Right, IJAR, 2016,. All rights reserved.
... Moreover, using various animal models, the destructive effect of oxidative stress on learning and memory has been reported [24]. Among the various areas of the brain, the cerebral cortex and hippocampus, which both play vital roles in learning and cognition, have shown the highest sensitivity to oxidative stress [25]. ...
Background:
The role of neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced memory and synaptic plasticity impairment was investigated.
Methods:
The rats were divided and treated as follows: (1) control (saline), (2) LPS, (3) 7NI (7-nitroindazole as a nNOS inhibitor)-LPS and (4) 7NI.
Results:
In a Morris water maze, the LPS group took a longer amount of time and traveled a greater distance to reach the platform, this was prevented by 7NI. Malondialdehyde (MDA) and nitric oxide (NO) metabolites in the hippocampus of the LPS group were higher while the total thiol, superoxide dismutase and catalase were lower than that of the controlled specimen. Pre-treatment using 7NI prevented the changes in the biochemical criteria. The slope and amplitude of the field excitatory post-synaptic potential (fEPSP) in the LPS group decreased, whereas in 7NI-LPS group they increased.
Conclusion:
It is suggested that inhibition of nNOS by 7NI improves the deleterious effects of LPS by reducing NO metabolites and the brain tissues oxidative damage.
... A variety of neurodegenerative diseases, including Alzheimer's disease (Richardson, 1993), Parkinson's disease (Olanow, 1993), amyotrophic lateral sclerosis (Olanow, 1993) and ...
Tumor necrosis factor (TNF) exerts its biological functions via two distinct receptors. Whereas the TNF receptor (TNFR) 1 mainly mediates inflammatory responses, the TNFR2 is involved in tissue protection and regeneration. Accordingly, TNF variants selectively activating TNFR2 could potentially be useful as therapeutic regimen in a variety of diseases. In this study, there was developed a TNFR2-specific agonist, which may be a promising therapeutic in immune- and neurodegenerative diseases. In addition, the molecular mechanisms of TNFR2 signaling and turnover at the membrane were further unrevealed.
Endocytosis is an important mechanism to regulate TNF signaling. In contrast to TNFR1, the relevance of receptor internalization for signaling as well as the fate and route of internalized TNFR2 is poorly understood. Upon generation of a human TNFR2-expressing mouse embryonic fibroblast cell line in a TNFR1-/-/TNFR2-/--background, I could demonstrate that TNFR2 was internalized together with its ligand and cytoplasmic binding partners. The internalization was dependent on a di-leucin motif in the cytoplasmic part of TNFR2 and the colocalization of the receptor-complex with clathrin suggested clathrin-mediated internalization of TNFR2. Internalization-defective TNFR2 mutants were capable to signal, i.e. activate NFkB, demonstrating that the di-leucin motif-dependent internalization is dispensable for this response. Therefore receptor internalization primarily seems to serve as a negative feed-back to limit TNF responses via TNFR2.
Soluble recombinant TNF is a strong mediator of inflammation, predominantly through TNFR1 activation, as soluble TNF is not sufficient to activate TNFR2. In contrast, the membrane-bound form of TNF (memTNF) fully activates both TNFRs. Therefore, TNFR2-specific therapeutics need to comply with two basic requirements: mimicry of memTNF and, in order to avoid dose limiting severe inflammatory responses, receptor selectivity. As a basis for the construction of a memTNF-mimetic, TNFR2-selective TNF variant, a single-chain TNF (scTNF) molecule was used, that consists of three TNF monomers fused by short peptide linkers. Introducing two amino acid exchanges (D143N/A145R) into a scTNF variant resulted in the loss of TNFR1 affinity under retention of TNFR2 binding. To mimic memTNF, such a receptor-selective single-chain TNF (scTNFR2) was linked to the tenascin C (TNC) trimerization domain, resulting in stabilized TNC-scTNFR2 nonamers with respect to the TNF domains. In vitro TNC-scTNFR2 demonstrated memTNF-mimetic activity and exclusively activated TNFR2.
TNC-scTNFR2-enhanced T cell activation was shown by the increased interleukin 2-dependent interferon gamma production. More revealing, TNC-scTNFR2 increased the number of regulatory FoxP3+/CD25+ T cells in cultures of human peripheral blood mononuclear cells, suggesting a potential role in downregulation of T cell immune responses. In cultures of primary astrocytes TNC-scTNFR2 induced the upregulation of ciliary neurotrophic factor, a neurotrophic factor, which enhances the formation of myelin. In addition, in in vitro cultures, TNC-scTNFR2 rescued differentiated neurons from hydrogen peroxide-induced cell death.
First in vivo studies on the pharmacokinetic behavior and potential systemic responses in huTNFR2-transgenic mice revealed that compared to TNF, TNC-scTNFR2 has a dramatically extended plasma half-life, yet shows no signs of systemic toxicity and thus is well tolerated even at doses several fold above the MTD of wildtype TNF. These results warrant further studies on the therapeutic usefulness of TNC-scTNFR2 in appropriate animal models of autoimmune and neurodegenerative diseases.
Age-related neurological disorders [ANDs] involve neurodegenerative diseases [NDDs] such as Alzheimer's disease [AD], the most frequent kind of dementia in elderly people, and Parkinson's disease [PD], and also other disorders like epilepsy and migraine. Although ANDs are multifactorial, Aging is a principal risk factor for them. The common and most main pathologic features among ANDs are inflammation, oxidative stress, and misfolded proteins accumulation. Since failing brains caused by ANDs impose a notable burden on public health and their incidence is increasing, a lot of works has been done to overcome them. Garlic, Allium sativum, has been used for different medical purposes globally and more than thousands of publications have reported its health benefits. Garlic and aged garlic extract are considered potent anti-inflammatory and antioxidants agents and can have remarkable neuroprotective effects. This review is aimed to summarize knowledge on the pharmacotherapeutic potential of garlic and its components in ANDs.
Age-related neurodegenerative diseases represent a major medical problem for modem society. As longevity of our population increases, these disorders could reach epidemic proportions. The key to understanding age-related neurodegenerative disorders is to determine why neurons degenerate and die in specific brain regions in different disorders. Major research is underway to understand the etiology and pathogenesis of these disorders to facilitate rational development of effective therapies. Numerous partially overlapping hypotheses about the pathogenesis of neurodegenerative diseases include genetic defects, altered membrane metabolism, trace element neurotoxicity, excitotoxicity, reduced energy metabolism, and free-radical-mediated damage. Accumulating evidence indicates that increased free-radical-mediated damage to cellular function contributes to the aging process and age-related neurodegenerative disorders. Indeed, increased free-radical-mediated damage relates closely to the reduced energy metabolism, trace element toxicity, and excitotoxicity hypotheses in neurodegeneration.
Fourteen novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine derivatives bearing benzimidazole moiety (7a‐n) have been synthesized using the one‐pot nitro reductive cyclization method. All the synthesized compounds were confirmed by ¹H nuclear magnetic resonance (¹H NMR), ¹³C NMR, fourier‐transform infrared (FT‐IR), mass spectrum, and elemental analyses. All the title compounds were subjected to in vitro antioxidant activity. The free radical scavenging activity of the compounds was examined using DPPH, nitric oxide, and superoxide radical scavenging methods. The results demonstrated that compound 3‐(2‐(3,4‐dimethoxyphenyl)‐1‐propyl‐1H‐benzo[d]imidazol‐5‐yl)‐6‐4‐tolyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine (7c) was potent in scavenging both DPPH and nitric oxide radical with IC50 values of 13.57 and 18.55 μg/ml when compared to the standard with IC50 values of 23.75 and 23.14 μg/ml, respectively, which was due to the presence of electron‐donating groups. The activity was found to decline when electron‐donating groups were replaced by electron‐withdrawing groups. Moderate scavenging activity was observed for the superoxide radical. Structure activity relationship and physiochemical properties were studied for all the derivatives.
The brain undergoes two aging programs: chronological and endocrinological. This is particularly evident in the female brain, which undergoes programs of aging associated with reproductive competency. Comprehensive understanding of the dynamic metabolic and neuroinflammatory aging process in the female brain can illuminate windows of opportunities to promote healthy brain aging. Bioenergetic crisis and chronic low-grade inflammation are hallmarks of brain aging and menopause and have been implicated as a unifying factor causally connecting genetic risk factors for Alzheimer’s disease and other neurodegenerative diseases. In this review, we discuss metabolic phenotypes of pre-menopausal, peri-menopausal, and post-menopausal aging and their consequent impact on the neuroinflammatory profile during each transition state. A critical aspect of the aging process is the dynamic metabolic neuro-inflammatory profiles that emerge during chronological and endocrinological aging. These dynamic systems of biology are relevant to multiple age-associated neurodegenerative diseases and provide a therapeutic framework for prevention and delay of neurodegenerative diseases of aging. While these findings are based on investigations of the female brain, they have a broader fundamental systems of biology strategy for investigating the aging male brain. Molecular characterization of alterations in fuel utilization and neuroinflammatory mechanisms during these neuro-endocrine transition states can inform therapeutic strategies to mitigate the risk of Alzheimer’s disease in women. We further discuss a precision hormone replacement therapy approach to target symptom profiles during endocrine and chronological aging to reduce risk for age-related neurodegenerative diseases.
The book’s introductory chapter outlines its ambitions, aims and objectives. Fish, fishing and fishing communities are perhaps among the most opaque and little-studied developmental ecosystems. Equally, North Korea is one of the most difficult to study and confusing research sites on the globe. In introducing this book, its shape and objectives, this chapter aims to give a coherent and comprehensive sense of how this opacity and difficulty might be overcome and managed. In particular, the chapter engages with the literature of vibrant, lively and non-human matters, as this is the lens through which the author seeks to explore the realm of fish, fisherpeople and fishing. Following the work of scholars such as Jane Bennett and Sarah Whatmore, the interactions and exchanges that mark out such a complex ‘web of life’ will be explored in a wide variety of scales, sites and situations. Vibrancy and liveliness of such fishing matter(s) will be considered in the context of both abundance and scarcity, vitality and degradation within this book and an introduction sensitive to thoughts and theories, which might bind these varied situations together is important to that consideration. Vital to this watery introduction to will be a sense of the nature of the web of life within which these vibrant matters function, especially in the political and politico-social sense of that web, focusing as it does on North Korea, a national polity possessed of its own peculiar, distinct and local form of politics. While Jason Moore, who coined the notion of the ‘web of life’ used within this book, sought to unpack the place and role of nature within a web of capitalist life, of course, North Korea is anything but a conventional space of capitalism. This book roots its analysis of Pyongyang’s ideology within that produced by Heonik Kwon and Byung-ho Chung, which holds it to be characterised by a theatric or charismatic politics recognisable to both Max Weber and Clifford Geertz. Finally, this introduction engages with the methodologies and literature of fishing histories and geographies across the globe. The watery terrains of this book, therefore, from North Korea and its neighbours are complex assemblages of the symbolic, constructed and co-produced as well as the concrete and the vibrant.
Alzheimer's disease, the leading cause of dementia in the elderly is characterized by the presence in the brain of senile plaques formed of insoluble fibrillar deposits of β-amyloid peptide. This peptide is normally produced in a monomeric soluble form and it is present in low concentrations in the blood and spinal fluid. At physiological concentrations, this peptide is a neurotrophic and neuroprotector factor; nevertheless, with aging and particularly in Alzheimer's disease this peptide accumulates, favors the formation of insoluble fibrils and causes neurotoxicity. β-amyloid peptide toxicity has been associated with the generation of free radicals that in turn promote lipid peroxidation and protein oxidation. Through the recognition of specific receptors such as the scavenger receptor, the β-amyloid peptide becomes internalizedin the form of aggregates. Independently of the way the peptide enters the cell, it generates oxidative stress that eventually triggers a state of neurotoxicity and cell death. Recent studies in our laboratory have shown the effect caused by an extracellular oxidative stress upon the internalization of the scavenger receptor. We have also demonstrated that the process of protein translation of molecules implicated in the mechanism of endocytosis through the scavenger receptor, such as the case of β-adaptin, is arrested in microglial cells treated with β-amyloid.
In this communication the diverse potential of various algal species is analysed in terms of ecological, economical and bioenergy production. As the available methods of pollution remediation and fertilizers are high in cost and are not friendly for the environment. The biochemical constituents of algae like protein, carbohydrates and lipids have been used in different industries of food, cosmetics and medicines. Algal protein is high in demands over the world due to its high nutrient value and organically produced nature. The algal biomass contains up to 50% oil contents in the form of triglycerides and can be easily converted to alkyl esters which may become good substitutes for petrochemical diesel. Due to the first organisms of food chain in aquatic ecosystems, algae have great ecological importance. Algae have also been found suitable for the remediation of contaminants (heavy metals, pesticides, dyes, etc.) from the polluted water bodies and this method is popularized as phycoremediation. The lipid extracted from algae has enormous potential to produce biodiesel which may become an important alternative to fossil fuels.
Brain is the most energetically demanding organ of the body, and is thus vulnerable to even modest decline in ATP generation. Multiple neurodegenerative diseases are associated with decline in mitochondrial function, e.g., Alzheimer’s, Parkinson’s, multiple sclerosis and multiple neuropathies. Genetic variances in the mitochondrial genome can modify bioenergetic and respiratory phenotypes, at both the cellular and system biology levels. Mitochondrial haplotype can be a key driver of mitochondrial efficiency. Herein, we focus on the association between mitochondrial haplotype and risk of late onset Alzheimer’s disease (LOAD). Evidence for the association of mitochondrial genetic variances/haplotypes and the risk of developing LOAD are explored and discussed. Further, we provide a conceptual framework that suggests an interaction between mitochondrial haplotypes and two demonstrated risk factors for Alzheimer’s disease (AD), apolipoprotein E (APOE) genotype and chromosomal sex. We posit herein that mitochondrial haplotype, and hence respiratory capacity, plays a key role in determining risk of LOAD and other age-associated neurodegenerative diseases. Further, therapeutic design and targeting that involve mitochondrial haplotype would advance precision medicine for AD and other age related neurodegenerative diseases.
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by an heterogeneous etiopathogenesis on a genetic basis. The most prominent neuropathological findings in AD are senile plaques, neurofibrillary tangles (NFT), amyloid deposition in neural tissues and vessels, synaptic loss and subsequent neuronal death (Cacabelos et al., 1993, 1995; Hardy and Allsop, 1991; Terry et al., 1991). However, other neurochemical mechanisms may also account for cell death and neurodegeneration in AD, including neuroimmune dysfunction, free radical formation, neurotransmitter deficits and alterations in brain calcium homeostasis (Cacabelos et al., 1994, 1995; Richardson, 1993). So, new approaches to AD treatment are oriented to search for agents acting on etiopathogenic events and pleiotropic compounds displaying multifactorial effects.
BACKGROUND: Along with aging, antioxidase activity decreases and oxygen-derived free radicals greatly accumulate, resulting in cellular senescence, or even cell death. This is manifested by hypomnesia and disordered metabolism of free radicals. Studies have reported that Longyanshen polysaccharides have the function of antioxidation and improved brain memory. OBJECTIVE: To observe the effects of Longyanshen polysaccharides on free radical metabolism in brain tissue to verify the anti-aging mechanisms in senescence accelerated-prone (SAMP8) mice. DESIGN, TIME AND SETTING: The randomized, controlled, biochemical experiment was performed in the Department of Pharmacology and Scientific Experimental Center of Guangxi Medical University (China) from September 2005 to January 2008. MATERIALS: Forty SAMP8 mice were randomized into four groups: SAMP8 control group, as well as low-, mid-, and high-dose polysaccharide, with 10 mice in each group. Ten senescence accelerated-resistant-prone (SAMR1) mice served as the normal control group. Longyanshen polysaccharides, extracted from the medical plant Longyanshen, were Supplied by the Department of Pharmacology, Guangxi Medical University. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malonaldehyde (MDA), nitric oxide (NO), and total protein test kitwere purchased from Nanjing Jiancheng Bioengineering Institute (China). METHODS: SAMP8 mice were used to establish a dementia animal model. SAMP8 and SAMR1 control mice were administered 30 mL/kg saline. The low-, middle-, and high-dose polysaccharide groups were administered 45, 90, and 180 mg/kg Longyanshen polysaccharides, respectively. Each group was treated by intragastric administration, once daily, for 50 continuous days. MAIN OUTCOME MEASURES: One hour after the last administration, mouse brain tissues were collected, and retro orbital blood sampling was performed. Spectrophotometry was used to measure SOD and GSH-Px activity, as well as MDA and NO concentration in sera and brains of SAMP8 mice. RESULTS: SOD and GSH-Px activity decreased significantly, and MDA and NO concentration increased significantly, in SAMP8 control group brain tissues, compared with the SAMP1 control group (P < 0.05). Compared with the SAMP8 control group, Longyanshen polysaccharide-treated groups exhibited enhanced SOD and GSH-Px activity, as well as decreased MDA and NO concentration, in serum and brain tissue (P < 0.05). Longyanshen polysaccharides exerted a similar effect on SOD, GSH-Px, MDA, and NO concentrations in serum and brain tissues of SAMP8 mice. CONCLUSION: Longyanshen polysaccharides scavenged free radicals effectively, reduced NO concentration and ameliorated NO toxicity, thereby influenced aging and stress, as well as improving memory capacity in the brain.
The exact cause of the pathogenesis of Alzheimer's disease (AD) is unknown. There is a growing body of evidence that oxidative stress may play a significant role in the slow and progressive neurodegeneration that is the hallmark of this disorder. We carried out a case-control study comparing peripheral blood markers of oxidative stress in a group of Alzheimer patients and elderly healthy control subjects. We measured plasma levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the peroxidation product malondialdehyde (MDA). Baseline measurements showed that individuals with AD have significantly higher levels of GSSG and MDA compared to controls (p= 0.002, 0.0003 respectively). There was no significant difference in GSH levels between the two groups. Using the Single Cell Gel Electrophoresis assay (the 'comet' assay), we also determined the DNA single strand breaks in freshly isolated lymphocytes. A statistically significant increase in mean basal DNA strand breaks was observed in AD subjects compared with elderly control subjects (p= 0.0001). In summary, the data presented in this work suggest that individuals with AD may be subject to increased oxidative stress and disturbed defence mechanisms. This is in broad agreement with findings from studies carried out in AD brain tissue, and in support of the hypothesis that oxidative stress may have an aetiological role in AD pathogenesis.
The aim of the study was to evaluate the effect of the extract obtained from fruits of Aronia melanocarpa (PA) containing anthocyanin antioxidants on lipid peroxidation in rats subjected to the exhaustive physical exercise. The animals were given PA intragastrically for four consecutive days and then they were forced to run to exhaustion on a treadmill set at the track speed of 28 m per min Three hours after completion of the exercise lipid peroxidation was assessed by estimating the concentration of the thiobarbituric acid reactive substances (TBARS) in the heart, liver and the red and white parts of the gastrocnemius muscle. In addition, the serum activity of creatine kinase was assessed. The time of the run to exhaustion in the control group of the animals (group C) was similar to that in rats fed the PA (group T). In the two groups of the animals the exercise led to increases in TBARS in all the organs tested except for the red part of gastrocnemius of the T rats. In fact, the level of TBARS in this part of the muscle was significantly (P<0.05) lower in the PA-fed animals than in the control rats. Application of PA did not affect the post-exercise rise in the serum CK activity. The results indicate that PA exhibit a minor antioxidant activity in rats subjected to exhaustive exercise.
Aqueous-methanolic (20:80) extract of stem-bark of Litchi chinensis Sonn. was fractionated with diethyl ether, ethyl acetate and n-butanol using solvent extraction technique, and then total phenols (TP), total flavonoides (TF) and total condensed tannins (TCT) were calculated for this extract and its organic fractions. Total phenolic compounds ranged from 145.2 ± 1.3-680.3 ± 1.2 mg GAE/g of sample, while total flavonoides and total condensed tannins ranged from 101.5 ± 1.4-210.4 ± 2.0 mg equivalent to catechin/g of sample and 95.7 ± 1.2-324.5 ± 0.8 mg equivalent to catechin/g of sample, respectively. Antioxidant potential of the extract and its fractions was evaluated using DPPH radical scavenging and phosphomolybdate assays. Ethyl acetate fraction scavenged maximum DPPH radical (78%, IC 50 = 15.3 μg/mL), close to BHT (80%, IC 50 = 12.4 μg/mL) while aqueous-methanolic extract showed the highest total antioxidant activity (1.09) as compared to its fractions relative to gallic acid. Agar well diffusion assay was also carried out to check the antibacterial activity against six different bacterial strains (Proteus mirabilis, Micrococcus luteus, Bacillus licheniformis, Nocardia asteroids, Salmonella typhimorium and Bacillus subtilis). The aqueous-methanolic extract showed the maximum growth inhibition (19.7 ± 0.9 mm, MIC = 1.2 mg/mL) against Bacillus subtilis. These results suggested the potential use of Litchi extracts as an antioxidant as well as antibacterial agent.
Garlic (Allium sativum) ranks the highest of all the herbal remedies consumed for their health benefits. Garlic, one of the oldest plants used in medicine, has been an important part of life for centuries, across cultures and millennia. Garlic has been used to spice food, fortify soldiers for war, cure colds, heal infections, and treat ailments ranging from heart disease to cancer and even the plague. Garlic has proven to have a broad range of health benefits and anti-aging effects, helping prevent disease and age-related pathological conditions. Scientific and clinical studies have shown that garlic can enhance immunity, protect against infection and inflammation, and help lower the risk of cancer, heart disease, and dementia, the most common form of which is Alzheimer's disease. From a medicinal point of view, and effectiveness in preventing age-related conditions, the stable water-soluble organosulfur compounds in garlic are highly effective. Present to some extent in fresh garlic, their level is increased by a process of aging. The extraction and aging process produces a high content of water-soluble organosulfur compounds, and converts unstable compounds, such as allicin, to stable compounds, thus increasing the antioxidant content of aged garlic extract (AGE), compared to fresh garlic. The major organosulfur compound in AGE is S-allyl cysteine. It is stable, has high antioxidant activity, and is highly bioavailable, with absorption of close to 98% into the circulation. S-allyl cystine is used for commercial standardization of the AGE products including tablets, capsules, and liquid forms.
The aim of this study was to evaluate the neuroprotective effects of kinetin (Kn) on oxidative damage induced by D-galactose (D-gal). In vitro, cultured astrocytes were distributed equally in different culture flasks to serve as control, model, and test groups. They were incubated respectively with 0 μM (model group), 50, 100 or 200 μM Kn along with 15 mM D-gal for 24 and 72 h, but cells in the control group received only normal medium. Activities of total-superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were measured by biochemical analysis. In vivo, mice were also randomly divided into control, model, and test groups. They were subcutaneously injected with D-gal (125 mg/kg), and administered with 0 (model group), and 10, 20 and 40 mg/kg Kn (test groups) per day simultaneously by gastric perfusion, but mice in the control group only received 0.4 ml physiologic saline solution per day by gastric perfusion. After 6 weeks, T- SOD and GSH-Px activities, and MDA levels in the brain tissue were assessed by biochemical analysis. Results show that both Dgal- treated astrocytes and mice brains displayed impaired antioxidant systems, an increase in MDA levels, and a decrease in T-SOD and GSH-Px activities. After Kn treatment, the changes of antioxidant enzymes activities and MDA levels were reversed both in vitro and in vivo. In conclusion, results of this study indicate that supplementation of Kn protects cultured astrocytes in vitro and mouse brain from Dgal- induced oxidative damage.
Inflammation and oxidative stress have important roles in memory impairment. The effect of 7-nitroindazole (7NI) on lipopolysaccharide (LPS)-induced memory impairment was investigated. Rats were used, divided into four groups that were treated as follows: (1) control (saline); (2) LPS; (3) 7NI-LPS; and (4) 7NI before passive avoidance (PA). In the LPS group, the latency for entering the dark compartment was shorter than in the controls (p < 0.01 and p < 0.001); while in the 7NI-LPS group, it was longer than in the LPS group (p < 0.01 and p < 0.001). Malondialdehyde (MDA) and nitric oxide (NO) metabolite concentrations in the brain tissues of the LPS group were higher than in the controls (p < 0.001 and p < 0.05); while in the 7NI-LPS group, they were lower than in the LPS group (p < 0.001 and p < 0.05, respectively). The thiol content in the brain of the LPS group was lower than in the controls (p < 0.001); while in the 7NI-LPS group, it was higher than in the LPS group (p < 0.001). It is suggested that brain tissue oxidative damage and NO elevation have a role in the deleterious effects of LPS on memory retention that are preventable using 7NI.
This chapter discusses brain iron to understand its possible role in the pathogenesis of the neurodegenerative process and the potential of developing a neuroprotective therapy based on the concept of iron chelation. Iron in a free form is highly reactive and capable of inducing cytotoxicity by way of oxidative damage. The abundance of transferrin in the plasma serves to ensure that free iron is not available to induce local tissue damage. Increased levels of iron have been noted in association with neurodegeneration in both Parkinson's disease (PD) and Alzheimer's disease (AD). Experimental models of Parkinsonism can involve iron-induced neurodegeneration. 6-Hydroxydopamine (6-OHDA) has been shown to release iron from ferritin and to promote ferritin-dependent lipid peroxidation. Iron levels are also increased at sites of degeneration in AD. Increased iron has been detected in the hippocampus, nucleus basalis, frontal cortex, and motor cortex of AD patients. The finding of increased iron in the area of neurodegeneration in a wide array of conditions also raises the possibility that it is a secondary phenomenon that occurs consequent to cell death of any aetiology.
Intense lipid peroxidation of brain synaptosomes initiated with Fenton's reagent (H2O2 + Fe2+) began instantly upon addition of Fe2+ and preceded detectable OH. formation. Although mannitol or Tris partially blocked peroxidation, concentrations required were 10(3)-fold in excess of OH. actually formed, and inhibition by Tris was pH dependent. Lipid peroxidation also was initiated by either Fe2+ or Fe3+ alone, although significant lag phases (minutes) and slowed reaction rates were observed. Lag phases were dramatically reduced or nearly eliminated, and reaction rates were increased by a combination of Fe3+ and Fe2+. In this instance, lipid peroxidation initiated by optimal concentrations of H2O2 and Fe2+ could be mimicked or even surpassed by providing optimal ratios of Fe3+ to Fe2+. Peroxidation observed with Fe3+ alone was dependent upon trace amounts of contaminating Fe2+ in Fe3+ preparations. Optimal ratios of Fe3+:Fe2+ for the rapid initiation of lipid peroxidation were on order of 1:1 to 7:1. No OH. formation could be detected with this system. Although low concentrations of H2O2 or ascorbate increased lipid peroxidation by Fe2+ or Fe3+, respectively, high concentrations of H2O2 or ascorbate (in excess of iron) inhibited lipid peroxidation due to oxidative or reductive maintenance of iron exclusively in Fe2+ or Fe3+ form. Stimulation of lipid peroxidation by low concentrations of H2O2 or ascorbate was due to the oxidative or reductive creation of Fe3+:Fe2+ ratios. The data suggest that the absolute ratio of Fe3+ to Fe2+ was the primary determining factor for the initiation of lipid peroxidation reactions.
Superoxide dismutase (SOD) activity was measured by seven assay methods. The nitrite method was found to be the best for our SOD assay kit. This method was then modified to give better sensitivity and minimize interference by coexisting protein, a factor which has been previously ignored. Hydroxylamine or its O-sulfonic acid, xanthine oxidase, hypoxanthine, EDTA, and the sample were incubated with or without KCN at pH 8.2, 37°C, for 30 min. Diazo dye-forming reagent was added and the absorption was measured at 550 nm. Human plasma and erythrocyte lysate from healthy adults and Down's syndrome patients were assayed by this SOD kit and by the cytochrome c method. Our kit gave 8.5 times higher sensitivity than the cytochrome c method. This high sensitivity allowed the use of a simple spectrophotometer and, moreover, only one dilution was needed to determine the SOD unit with the help of our formulas. Good recovery, reproducibility, and stability of reagents were demonstrated.
Radicals are species containing one or more unpaired electrons, such as nitric oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2.- and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron or copper ions. An important form of antioxidant defense is the storage and transport of iron and copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e.g., by ischemia or trauma, can cause increased metal ion availability and accelerate free radical reactions. This may be especially important in the brain because areas of this organ are rich in iron and CSF cannot bind released iron ions. Oxidative stress on nervous tissue can produce damage by several interacting mechanisms, including increases in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminum and in damage to the substantia nigra in patients with Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be used in the design of antioxidants for therapeutic use.
An assay procedure is described in which blood cell glutathione peroxidase may be accurately measured by a direct spectrophotometric procedure. Glutathione peroxidase activity is found to be associated with a relatively stable, nondialyzable, heat-labile, intracellular component which is separable from hemoglobin, by gel filtration and ammonium sulfate precipitation. The activity appears to be dependent upon active sulfhydryl groups and is unaffected by low concentrations of azide, cyanide, or ferricyanide.
The involvement of iron in lipid peroxidation. Importance of ferric ratios in initiation Reevaluation of assay methods and establishment of kit for superoxide dismutase activity
- J M Braughler
- L A Duncan
- R L Chase
BRAUGHLER, J. M., L. A. DUNCAN & R. L. CHASE. 1986. The involvement of iron in lipid peroxidation. Importance of ferric ratios in initiation. J. Biol. Chem. YOANAGUI, Y. 1984. Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal. Biochem. 132:290-296.