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Representative photomicrographs of frontal cerebral cortex and histomorphometry of degenerated cortical neurones in treated rats
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Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochemical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone...
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Citations
... In the present study, the administration of MWCNTs alone inhibited AChE activity in the mouse brain. Adedara et al. [39] also reported a similar inhibitory effect for MWCNTs on AChE activity with locomotor disturbance in rats. Increasing the production of free radicals could damage different molecules within the cell. ...
... This implies repression of their functions which could result in free radicals accumulation and oxidative stress damage. Similarly, GSH, SOD, and CAT levels were reduced in the cerebral cortex, cerebellum, striatum, hippocampus, liver, spleen, and kidney of rats injected with MWCNTs [2,21,39,40]. When the endogenous antioxidant defense system is disrupted, cell components, particularly the cell membrane which is rich in phospholipid, would be damaged by excessive release of free radicals. ...
... The reduction in the antioxidant status reported in our study was coupled with the accumulation of MDA in the brain of mice injected with MWCNTs. Consistent with these results, MWCNT-treated rodents showed higher ROS production in their brain [14,39], kidneys [2], and spleen [21]. The large surface area of CNTs plays an important role in ROS overproduction [43]. ...
Recently, we reported that quercetin (Que) could alleviate immunotoxicity induced by pristine multi-walled carbon nanotubes (MWCNTs) in mice. In the present study, we explored whether Que could also relieve MWCNTs-induced neurotoxicity. MWCNTs injection induced a dose-dependent neurotoxic effect in mice as evidenced by increased oxidative stress, inflammation, and pyroptosis in the brain. However, treatment with Que ameliorated MWCNTs-induced neurotoxicity as revealed by 1) elevated acetylcholinesterase (AChE) activity, 2) reduced lipid peroxidation biomarker malondialdehyde (MDA), 3) improved antioxidant status as indicated by increased levels of reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), as well as upregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes, 4) decreased levels and expression of inflammatory biomarkers [nitric oxide (NO), interleukin 1 beta (IL1ß), tumor necrosis factor-alpha (TNFα), and nuclear factor kappa B (NF-κB)], 5) downregulated expression of pyroptosis-related genes [nod-like receptor protein inflammasome 3 (Nlrp3) and caspase 1 (Casp1)] but with no effect on the apoptotic Casp3 gene, 6) minimized axonal degeneration and number of microglia in the cerebral medulla, and 7) diminished the number of degenerated neurons in hippocampus and cerebellum. Taken together, Que could ameliorate MWCNT-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-pyroptotic mechanisms.
... (Moringaceae) leaf extract or its bioactive compound, moringin, can be investigated in animal models of movement disorder and the outcome of this study can provide its suitability in future clinical use. Kolaviron, a natural flavonoid obtained from the seeds of Garcinia kola Heckel (Guttiferae) that is found in Cameroon and some other African countries, is used as a traditional medicine to treat the common cold, coughs, fever, and similar diseases [124]. Kolaviron showed anti-inflammatory, anti-colitis, antioxidant effects and prevented genotoxicity [124,125]. ...
... Kolaviron, a natural flavonoid obtained from the seeds of Garcinia kola Heckel (Guttiferae) that is found in Cameroon and some other African countries, is used as a traditional medicine to treat the common cold, coughs, fever, and similar diseases [124]. Kolaviron showed anti-inflammatory, anti-colitis, antioxidant effects and prevented genotoxicity [124,125]. Kolaviron prevented multi-walled carbon nanotubes (MWCNTs)-induced neurotoxicity (as shown with reduced locomotor activities) in rats [124]. In this study, 10-week-old male Wistar rats treated with kolaviron (100 mg/kg/day, oral) over a period of 15 days prevented neurotoxicity (defined as reduced exploratory and locomotor activities, such as total distance traveled, increased horizontal and turning behavior) induced by MWCNTs (1.0 mg/kg/day, intraperitoneal injections). ...
... Kolaviron showed anti-inflammatory, anti-colitis, antioxidant effects and prevented genotoxicity [124,125]. Kolaviron prevented multi-walled carbon nanotubes (MWCNTs)-induced neurotoxicity (as shown with reduced locomotor activities) in rats [124]. In this study, 10-week-old male Wistar rats treated with kolaviron (100 mg/kg/day, oral) over a period of 15 days prevented neurotoxicity (defined as reduced exploratory and locomotor activities, such as total distance traveled, increased horizontal and turning behavior) induced by MWCNTs (1.0 mg/kg/day, intraperitoneal injections). ...
Nanomedicines emerged from nanotechnology and have been introduced to bring advancements in treating multiple diseases. Nano-phytomedicines are synthesized from active phytoconstituents or plant extracts. Advancements in nanotechnology also help in the diagnosis, monitoring, control, and prevention of various diseases. The field of nanomedicine and the improvements of nanoparticles has been of keen interest in multiple industries, including pharmaceutics, diagnostics, electronics, communications, and cosmetics. In herbal medicines, these nanoparticles have several attractive properties that have brought them to the forefront in searching for novel drug delivery systems by enhancing efficacy, bioavailability, and target specificity. The current review investigated various therapeutic applications of different nano-phytopharmaceuticals in locomotor, dermal, reproductive, and urinary tract disorders to enhance bioavailability and efficacy of phytochemicals and herbal extracts in preclinical and in vitro studies. There is a lack of clinical and extensive preclinical studies. The research in this field is expanding but strong evidence on the efficacy of these nano-phytopharmaceuticals for human use is still limited. The long-term efficacy and safety of nano-phytopharmaceuticals must be ensured with priority before these materials emerge as common human therapeutics. Overall, this review provides up-to-date information on related contemporary research on nano-phytopharmaceuticals and nano-extracts in the fields of dermatological, urogenital, and locomotor disorders.
... (Moringaceae) leaf extract or its bioactive compound, moringin, can be investigated in animal models of movement disorder and the outcome of this study can provide its suitability in future clinical use. Kolaviron, a natural flavonoid obtained from the seeds of Garcinia kola Heckel (Guttiferae) that is found in Cameroon and some other African countries, is used as a traditional medicine to treat the common cold, coughs, fever, and similar diseases [124]. Kolaviron showed anti-inflammatory, anti-colitis, antioxidant effects and prevented genotoxicity [124,125]. ...
... Kolaviron, a natural flavonoid obtained from the seeds of Garcinia kola Heckel (Guttiferae) that is found in Cameroon and some other African countries, is used as a traditional medicine to treat the common cold, coughs, fever, and similar diseases [124]. Kolaviron showed anti-inflammatory, anti-colitis, antioxidant effects and prevented genotoxicity [124,125]. Kolaviron prevented multi-walled carbon nanotubes (MWCNTs)-induced neurotoxicity (as shown with reduced locomotor activities) in rats [124]. In this study, 10-week-old male Wistar rats treated with kolaviron (100 mg/kg/day, oral) over a period of 15 days prevented neurotoxicity (defined as reduced exploratory and locomotor activities, such as total distance traveled, increased horizontal and turning behavior) induced by MWCNTs (1.0 mg/kg/day, intraperitoneal injections). ...
... Kolaviron showed anti-inflammatory, anti-colitis, antioxidant effects and prevented genotoxicity [124,125]. Kolaviron prevented multi-walled carbon nanotubes (MWCNTs)-induced neurotoxicity (as shown with reduced locomotor activities) in rats [124]. In this study, 10-week-old male Wistar rats treated with kolaviron (100 mg/kg/day, oral) over a period of 15 days prevented neurotoxicity (defined as reduced exploratory and locomotor activities, such as total distance traveled, increased horizontal and turning behavior) induced by MWCNTs (1.0 mg/kg/day, intraperitoneal injections). ...
Citation: Rajagopal, M.; Paul, A.K.; Lee, M.-T.; Joykin, A.R.; Por, C.-S.; Mahboob, T.; Salibay, C.C.; Torres, M.S.; Guiang, M.M.M.; Rahmatullah, M.; et al. Phytochemicals and Nano-Phytopharmaceuticals Use in Skin, Urogenital and Locomotor Disorders: Are We There? Plants 2022, 11, 1265. https://doi.org/10.3390/ plants11091265 Academic Editors: Konstantinos Gardikis and Ioannis Mourtzinos
... Several animal and clinical evidence have demonstrated the biological relevance of KV in suppressing conditions associated with inflammation and redox imbalance. [17] In the past decade, emerging data are confirming that neuronal injury can also be prevented or repaired by KV. [39][40][41][42] Recently, we provided a proof of concept that KV could offer a potent neuroprotective advantage for the prevention and management of PD. [14] In the study, we showed that KV suppressed sensorimotor imbalance, loss of dopaminergic neurons in the SNc and striatal pathology in rotenone mice through a mechanism related to its antioxidant and antiinflammatory properties. [14] However, given the intermediary role of Nrf2 in regulating the endogenous cytoprotective antioxidant capacity, and a previous report indicating that attenuation of LPS-induced neuroinflammation in microglial BV2 and neuronal HT22 co-culture system by KV is dependent on Nrf2/ARE, we hypothesized that the demonstrated neuroprotective ability of KV may involve Nrf2 signaling. ...
Objectives
Parkinson’s disease (PD) is the most prevalent movement disorder. Available therapies are palliative with no effect on disease progression. We have previously demonstrated that kolaviron (KV), a natural anti-inflammatory and antioxidant agent, suppressed behavioral defect, redo-inflammation, and nigrostriatal pathology in rotenone PD model. The present study investigates the neuroprotective effect of KV focusing on DJ-1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.
Material and Methods
All-trans retinoic acid (ATRA, 10 mg/kg/day) was used to inhibit Nrf2. PD was established with four doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (20 mg/kg) at 2 h interval. MPTP mice were pre-treated with either KV (200 mg/kg/day), ATRA or both for 7 days before MPTP. Mice were evaluated for locomotor defects and indices of oxidative stress, neuroinflammation and neurotransmission as well as pathological tyrosine hydroxylase expression PD were evaluated in the striatum.
Results
ATRA alone in mice did not exhibit neurobehavioral defect but caused striatal toxicity, mild nigrostriatal pathology, significant nitrosative stress, and Nrf2 cascade inhibition. KV+ATRA mice were slow in movement with frequent short-lived interruptions and oxidative striatal pathology. ATRA aggravated MPTP-associated locomotor incompetence and could not prevent nigrostriatal toxicity with evident vacuolated striosome and pyknotic/degenerating dopaminergic neurons. MPTP induced acute locomotor, exploratory, and motor incompetence, which was prevented by KV treatment. In addition, KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal nitrosative stress, and oxidative damage with elevated DJ-1 level, potentiated Nrf2/NAD(P)H; quinone oxidoreductase-1 cytoprotective capacity, reduced Kelch-like ECH-associated protein 1 expression, and limited striatal pathology. However, ATRA treatment attenuated all the protective effects of KV on MPTP-challenged mice. Meanwhile, other ATRA-combinations elicited significant DJ-1 and Nrf2 induction but are associated striatal toxicity/pathology.
Conclusion
This suggests that KV may be conferring protection through a yet-undetermined DJ-1 downstream cytoprotective effect dependent on the KV-mediated attenuation of oxidative environment.
... Joint exposure to atrazine and ciprofloxacin amplified the oxidative stress condition induced by atrazine alone and ciprofloxacin alone in the midgut, hemolymph, and head of the exposed insects as evidenced by marked elevation in RONS and LPO levels cum diminution in antioxidant enzymes activities and GSH level in the current study. Cellular antioxidants are primarily responsible for the scavenging of free radicals before initiating oxidative and nitrosative stress mechanism leading to cellular damage (Poprac et al. 2017;Adedara et al. 2020b). The significant reduction in the CAT and SOD activities exhibited by insects singly and jointly exposed to atrazine and ciprofloxacin suggests a suppression of their antioxidant defense actions to neutralize cytotoxic radicals in the midgut, hemolymph, and head of the exposed insects. ...
The global detection of ciprofloxacin and atrazine in soil is linked to intensive anthropogenic activities in agriculture and inadvertent discharge of industrial wastes to the environment. Nauphoeta cinerea is a terrestrial insect with cosmopolitan distribution and great environmental function. The current study probed the neurobehavioral and cellular responses of N. cinerea singly and jointly exposed to atrazine (1.0 and 0.5 μg g−1 feed) and ciprofloxacin (0.5 and 0.25 μg g−1 feed) for 63 days. Results demonstrated that the reductions in the body rotation, maximum speed, turn angle, path efficiency, distance traveled, episodes, and time of mobility induced by atrazine or ciprofloxacin per se was exacerbated in the co-exposure group. The altered exploratory and locomotor in insects singly and jointly exposed to ciprofloxacin and atrazine were verified by track plots and heat maps. Furthermore, we observed a decrease in acetylcholinesterase and anti-oxidative enzyme activities with concomitant elevation in the levels of lipid peroxidation, nitric oxide, and reactive oxygen and nitrogen species were significantly intensified in the midgut, hemolymph, and head of insects co-exposed to ciprofloxacin and atrazine. In conclusion, exposure to binary mixtures of ciprofloxacin and atrazine elicited greater locomotor and exploratory deficits than upon exposure to the individual compound by inhibiting acetylcholinesterase activity and induction of oxido-inflammatory stress responses in the insects. N. cinerea may be a usable model insect for checking contaminants of ecological risks.
... Several studies focused on assessing CN toxicity (in vivo and in vitro) based on different experimental models, including microorganisms, animals (including humans) and plants (Filho et al., 2014;Andrade et al., 2014;Maes et al., 2014;Ghosh et al., 2015a, b;Girardi et al., 2017;Beard et al., 2018;Chen et al., 2018;Snyder-Talkington et al., 2019;Requardt et al., 2019;Zhao et al., 2019;Adeyemi et al., 2019;Lee et al., 2019;Knudsen et al., 2019;Farombi et al., 2020;Cheng et al., 2020;Pandey et al., 2020;Gomes et al., 2021). On the other hand, the numerical disparity between studies about different CN types is clear. ...
The toxicity of carbon-based nanomaterials (CNs) has been observed in different organisms; however, little is known about the impact of water polluted with carbon nanofibers (CNFs) on reptiles. Thus, the aim of the current study was to assess the chronic effects (7.5 months) of 1 and 10 mg/L of CNF on Podocnemis expansa (Amazon turtle) juveniles (4 months old) based on different biomarkers. Increased total organic carbon (TOC) concentrations observed in the liver and brain (which suggests CNF uptake) were closely correlated to changes in REDOX systems of turtles exposed to CNFs, mainly to higher nitrite, hydrogen peroxide and lipid peroxidation levels. Increased levels of antioxidants such as total glutathione, catalase and superoxide dismutase in the exposed animals were also observed. The uptake of CNFs and the observed biochemical changes were associated with higher frequency of erythrocyte nuclear abnormalities (assessed through micronucleus assays), as well as with both damage in erythrocyte DNA (assessed through comet assays) and higher apoptosis and necrosis rates in erythrocytes of exposed turtles. Cerebral and hepatic acetylcholinesterase (AChE) increased in turtles exposed to CNFs, and this finding suggested the neurotoxic effect of these nanomaterials. Data in the current study reinforced the toxic potential of CNFs and evidenced the biochemical, mutagenic, genotoxic, cytotoxic, and neurotoxic effects of CNFs on P. expansa.
... However, one must take into account that their increased use almost inevitably leads to their discharge into the environment and, consequently, to (eco)toxicological risk (Cheng et al., 2007;Du et al., 2013;Myojo and Ono-Ogasawara, 2018). This has been demonstrated in different studies, involving different organisms (e.g.: microorganisms, animal models (including humans) and plants (Filho et al., 2014;Andrade et al., 2014;Maes et al., 2014;Ghosh et al., 2015;Girardi et al., 2017;Beard et al., 2018;Chen et al., 2018;Snyder-Talkington et al., 2019;Requardt et al., 2019;Zhao et al., 2019;Adeyemi et al., 2019;Lee et al., 2019;Knudsen et al., 2019;Farombi et al., 2020;Cheng et al., 2020;Pandey et al., 2020;Gomes et al., 2021)). Overall, these studies gather sufficient evidence to justify the need of paying closer attention to the potential toxicological risks posed by NCs. ...
Carbon-based materials have been considered very promising for the technological industry due to their unique physical and chemical properties, namely: ability to reduce production costs and to improve the efficiency of several products. However, there is little information on what is the level of exposure that leads to adverse effects and what kind of effects is expected in aquatic biota. Thus, the aim of the present study was to evaluate the toxicity of carbon nanofibers (CNFs) in dragonfly larvae (Aphylla williamsoni) based on predictive oxidative-stress biomarkers, antioxidant activity reduction and neurotoxicity. After ephemeral models' exposure to CNFs (48 h; at 500 μg/L), data have shown that these pollutants did not change larvae's nutritional status given the concentration of total soluble carbohydrates, total proteins and triglycerides in them. However, the levels of both nitric oxide and substances reactive to thiobarbituric acid (lipid peroxidation indicators) have increased and the antioxidant activity based on total thiol levels and on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (%) has reduced, and it suggests REDOX imbalance induction by CNFs. In addition, larvae exposed to these pollutants showed significant acetylcholinesterase activity reduction in comparison to the control group. Thus, the present study has brought further knowledge about how carbon-based materials can affect benthic macroinvertebrates and emphasized their ecotoxicological potential in freshwater environments.
... However, there is a growing scientific interest on the use MWCNTs in recent years because of the health concerns associated with undue human and animal exposure (Kobayashi et al. 2017;Fukushima et al. 2018). For instance, MWCNTs administration elicits adverse effects on the brain, liver, and reproduction in zebrafish and rats (Li et al. 2015;Adedara et al. 2018Adedara et al. , 2020. Earlier investigators reported that nanomaterials affect reproduction and development through direct and indirect means (Ema et al. 2016a). ...
... The current investigation adopted intraperitoneal injection because it delivers a greater drug concentration with a minor systemic toxicity in comparison with other routes of administration (Shimada et al. 2005;Ema et al. 2016b). A dose of 1 mg/kg pure MWCNTs was selected because it is an environmentally relevant concentration which reportedly caused significant oxidative stress and histological lesions in the different organs whereas 50 and 100 mg/kg of kolaviron were selected based on their effective pharmacological data from preliminary studies and earlier published studies from our laboratory (Akinmoladun et al. 2015;Farombi et al. 2016;Adedara et al. 2018;Adedara et al. 2020). The final body weights of the animals were recorded 24 h following the last treatment. ...
Reproductive toxicity associated with excessive exposure to multi-walled carbon nanotubes (MWCNTs), which are commonly used in medicine as valuable drug delivery systems, is well documented. Kolaviron, a bioflavonoid isolated from Garcinia kola seeds, elicits numerous health beneficial effects related to its anti-inflammatory, anti-genotoxic activities, anti-apoptotic, and antioxidant properties. However, information on the role of kolaviron in MWCNTs-induced reproductive toxicity is not available in the literature. Herein, we assessed the protective effects of kolaviron on MWCNTs-induced dysfunctional reproductive axis in rats following exposure to MWCNTs (1 mg/kg) and concurrent treatment with kolaviron (50 or 100 mg/kg body weight) for 15 successive days. Results showed that MWCNTs-induced dysfunctional reproductive axis as evidenced by deficits in pituitary and testicular hormones, marker enzymes of testicular function, and sperm functional characteristics were abrogated in rats co-administered with kolaviron. Moreover, co-administration of kolaviron-abated MWCNTs-induced inhibition of antioxidant enzyme activities increases in oxidative stress and inflammatory indices. This is evidenced by diminished levels of tumor necrosis factor-alpha, nitric oxide, lipid peroxidation, reactive oxygen, and nitrogen species as well as reduced activity of myeloperoxidase in testes, epididymis, and hypothalamus of the rats. Biochemical data on the chemoprotection of MWCNTs-induced reproductive toxicity were corroborated by histological findings. Taken together, kolaviron suppressed dysfunctional reproductive axis associated with MWCNTs exposure via abrogation of oxidative stress and inflammation in male rats.
... Therefore, it explains the growing number of publications aimed at assessing CN toxicity, among them one finds occupational toxicology (Beard et al., 2018), in-vitro (Snyder-Talkington et al., 2019;Requardt et al., 2019;Zhao et al., 2019;Cheng et al., 2020;Adeyemi et al., 2019) and in-vivo studies based on different experimental models such as Mus musculus and Rattus norvegicus Knudsen et al., 2019;Farombi et al., 2020), Drosophila melanogaster (Andrade et al., 2014 ;Pandey et al., 2020), Danio rerio (Cheng et al., 2007;Filho et al., 2014;Maes et al., 2014;Girardi et al., 2017); plants (Andrade et al., 2014;Ghosh et al., 2015), microorganisms , among others. Overall, these studies and so many others available in the literature [see review in Chen et al. (2018)] have shown that the toxic effects of CNs comprise growth inhibition and destruction of plants' vegetative parts, changes in animal embryos' development and growth, as well as pulmonary, mutagenic, cytotoxic, genotoxic changes and reduced microbial diversity. ...
Although the toxicity of carbon-based nanomaterials has already been demonstrated in several studies, their transfer in the food chain and impact on the upper trophic level remain unexplored. Thus, based on the experimental food chain “Eisenia fetida → Danio rerio → Oreochromis niloticus”, the current study tested the hypothesis that carbon nanofibers (CNFs) accumulated in animals are transferred to the upper trophic level and cause mutagenic and cytotoxic changes. E. fetida individuals were exposed to CNFs and offered to D. rerio, which were later used to feed O. niloticus. The quantification of total organic carbon provided evidence of CNFs accumulation at all evaluated trophic levels. Such accumulation was associated with higher frequency of erythrocyte nuclear abnormalities such as constricted erythrocyte nuclei, vacuole, blebbed, kidney-shaped and micronucleated erythrocytes in Nile tilapia exposed to CNFs via food chain. The cytotoxic effect was inferred based on the smaller size of the erythrocyte nuclei and on the lower “nuclear/cytoplasmic” area ratio in tilapia exposed to CNFs via food chain. Our study provided pioneering evidence about CNFs accumulation at trophic levels of the experimental chain, as well as about the mutagenic and cytotoxic effect of these materials on O. niloticus.
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized of cognitive dysfunction. AD is believed to be a global menace with an estimated fourfold increase in prevalence by the year 2050. This increasing prevalence is linked to the unavailability of efficient treatment to halt the disease progression. While several hypotheses have been postulated on AD, oxidative stress, a state of an imbalance between antioxidant and free radical generation, has long been implicated in the pathogenesis of age-dependent late-onset AD. This state induces cognitive decline by stimulating neuronal damage, notably involving increased free radical production, and mitochondrial dysfunction. Pharmacological agents used in AD management have serious adverse effects and inability to halt disease progression. This has led to the emergence of naturally occurring neuroprotective phytochemical agents and herbal supplements as therapeutic option agents. Indeed, emerging studies have revealed the neuroprotective potential of different African herbal products, containing bioflavonoid compounds with central nervous system permeability and high antioxidant actions. Given this background, this chapter aims to discuss some of these African antioxidant bioflavonoids\\nutraceuticals, their neuroprotective functions against different epigenetic-derived oxidative stress, and ways ahead to facilitate their translation from “bench to bedside” as primary intervention or co-adjuvant therapies for AD treatment.
