Figure - available from: Molecular Neurobiology
This content is subject to copyright. Terms and conditions apply.
Structure components of various types H2S salts and donors. a Sulfide salts. b Phosphorodithioate derivatives. c Derivatives of Allium sativum extracts. d H2S-releasing hydrids
Source publication
Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, H2S is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, H2S has been found to induce the formation of long-term potential in neuronal ce...
Citations
... Hydrogen sulfide (H 2 S) is now a well-recognized gas transmitter after nitric oxide (NO) and carbon monoxide (CO), and it is endogenously produced in the brain and other various human organ tissues Wang (2002). Many studies have revealed that H 2 S controls the progression of physiopathological conditions such as Parkinson's disease Cao et al. (2018) and Alzheimer's disease Eto et al. (2002). H 2 S is a small molecule gas that can easily cross various biological membranes and has a wide range of targets. ...
Background
In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function.
Methods
Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value.
Results
Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05).
Conclusion
The results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function.
... Moreover, MPP + , which is used to induce PD, is known to elevate inflammatory mediators like Interferon gamma (IFN-γ), Tumor necrosis factor alpha (TNF-α), and interleukin-1 β (IL-1β) in microglia, and this elevation was greatly suppressed by potassium channel opener pinacidil [97]. Another agent that has been recently tried in the PD models is H 2 S. It exerts its anti-apoptotic effect on the dopamineproducing neurons of the substantia nigra by the opening of K ATP channels in the mitochondria, which in turn plays a role in the maintenance of the mitochondrial integrity [98]. ...
Parkinson’s disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive. With the aging population set to increase, a number of PD cases are expected to shoot up in the coming times. Hence, there is a need to look for new molecular targets that could be investigated both preclinically and clinically for PD treatment. Among these, several ion channels and metal ions are being studied for their effects on PD pathology and the functioning of dopaminergic neurons. Ion channels such as N-methyl-D-aspartate (NMDA), γ-aminobutyric acid A (GABAA), voltage-gated calcium channels, potassium channels, HCN channels, Hv1 proton channels, and voltage-gated sodium channels and metal ions such as mercury, zinc, copper, iron, manganese, calcium, and lead showed prominent involvement in PD. Pharmacological agents have been used to target these ion channels and metal ions to prevent or treat PD. Hence, in the present review, we summarize the pathophysiological events linked to PD with an emphasis on the role of ions and ion channels in PD pathology, and pharmacological agents targeting these ion channels have also been listed.
... There are numerous reports on the potential application of H 2 S in conditions like Alzheimer's disease [34], Parkinson's disease [35], intracellular hemorrhage [36], traumatic brain injury [37], myocardial ischemia/reperfusion injury [38], myocardial fibrosis [39], atherosclerosis [40], hepatic disorders [41], breast cancer [42], glaucoma [43], retinopathy [44], macular degeneration [45] and cataract [46]. The most investigated H 2 S donor, GYY 4137, exhibited relaxation of arteries, precontracted using phenylephrine in the concentration range of 100 nM to 100 mM with an IC 50 value of 13.4 ± 1.9 mM [47]. ...
Background: Hydrogen sulfide (H 2 S), an endogenous gasotransmitter, has potential applications in several conditions. However, its quantification in simulated physiological solutions is a major challenge due to its gaseous nature and other physicochemical properties. Aim: This study was designed to compare four commonly used H 2 S detection and quantification methods in aqueous solutions. Methods: The four techniques compared were one colorimetric, one chromatographic and two electrochemical methods. Results: Colorimetric and chromatographic methods quantified H 2 S in millimolar and micromole ranges, respectively. The electrochemical methods quantified H 2 S in the nanomole and picomole ranges and were less time-consuming. Conclusion: The H 2 S quantification method should be selected based on the specific requirements of a research project in terms of sensitivity, response time and cost-effectiveness.
... The metabolism of H 2 S is involved in neurodegenerative disorders, including PD. Evidence suggests that H 2 S production is impaired in the progression of PD (Cao et al. 2018). Hu et al. have shown that H 2 S levels were lower in rats lesioned unilaterally in the striatum with 6-hydroxydopamine (a PD rat model) in contrast with sham-operated rats (Hu et al. 2010). ...
... Four enzymes are responsible for H 2 S biosynthesis in the brain, including CBS, CSE, 3-mercaptopyruvate sulfur transferase, which acts together with cysteine aminotransferase (3-MPST/CAT) or with D-amino acid oxidase (3-MPST/ DAO) (Chen et al. 2015). CBS and CSE generate H 2 S in the cytosol and are pyridoxal-5′ phosphate (PLP)-dependent enzymes, while 3MST produces H 2 S in mitochondria and is PLP-independent (Cao et al. 2018). ...
The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H2S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine β-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.
... Abnormal levels of H 2 S and its metabolites have been identified in many studies in PD. Thus, it was shown that the level of endogenous H 2 S significantly decreased in the substantia nigra (SN) in PD, and the use of H 2 S donors contributed to the neuroprotective effect and reduced the death of dopaminergic neurons in this pathological condition [270]. The protective effect of H 2 S has been shown in various PD models in vitro and in vivo [271]. ...
Injuries of the central (CNS) and peripheral nervous system (PNS) are a serious problem of the modern healthcare system. The situation is complicated by the lack of clinically effective neuroprotective drugs that can protect damaged neurons and glial cells from death. In addition, people who have undergone neurotrauma often develop mental disorders and neurodegenerative diseases that worsen the quality of life up to severe disability and death. Hydrogen sulfide (H2S) is a gaseous signaling molecule that performs various cellular functions in normal and pathological conditions. However, the role of H2S in neurotrauma and mental disorders remains unexplored and sometimes controversial. In this large-scale review study, we examined the various biological effects of H2S associated with survival and cell death in trauma to the brain, spinal cord, and PNS, and the signaling mechanisms underlying the pathogenesis of mental illnesses, such as cognitive impairment, encephalopathy, depression and anxiety disorders, epilepsy and chronic pain. We also studied the role of H2S in the pathogenesis of neurodegenerative diseases: Alzheimer's disease (AD) and Parkinson's disease (PD). In addition, we reviewed the current state of the art study of H2S donors as neuroprotectors and the possibility of their therapeutic uses in medicine. Our study showed that H2S has great neuroprotective potential. H2S reduces oxidative stress, lipid peroxidation, and neuroinflammation; inhibits processes associated with apoptosis, autophagy, ferroptosis and pyroptosis; prevents the destruction of the blood-brain barrier; increases the expression of neurotrophic factors; and models the activity of Ca2+ channels in neurotrauma. In addition, H2S activates neuroprotective signaling pathways in psychiatric and neurodegenerative diseases. However, high levels of H2S can cause cytotoxic effects. Thus, the development of H2S-associated neuroprotectors seems to be especially relevant. However, so far, all H2S modulators are at the stage of preclinical trials. Nevertheless, many of them show a high neuroprotective effect in various animal models of neurotrauma and related disorders. Despite the fact that our review is very extensive and detailed, it is well structured right down to the conclusions, which will allow researchers to quickly find the proper information they are interested in.
... Similarly, overexpression of CBS or use of H 2 S donors in mouse models of PD affords neuroprotection (Cao et al., 2018;Jiang et al., 2022;Sarukhani et al., 2018;Xue & Bian, 2015;Yin et al., 2017). Although there are numerous instances of the neuroprotective effects of H 2 S, the underlying mechanisms are still unknown. ...
The gaseous neurotransmitter hydrogen sulfide (H2 S) exerts neuroprotective efficacy in the brain via post-translational modification of cysteine residues by sulfhydration, also known as persulfidation. This process is comparable in biological impact to phosphorylation and mediates a variety of signaling events. Unlike conventional neurotransmitters, H2 S cannot be stored in vesicles due to its gaseous nature. Instead, it is either locally synthesized or released from endogenous stores. Sulfhydration affords both specific and general neuroprotective effects and is critically diminished in several neurodegenerative disorders. Conversely, some forms of neurodegenerative disease are linked to excessive cellular H2 S. Here, we review the signaling roles of H2 S across the spectrum of neurodegenerative diseases, including Huntington's disease, Parkinson's disease, Alzheimer's disease, Down syndrome, traumatic brain injury, the ataxias, and amyotrophic lateral sclerosis, as well as neurodegeneration generally associated with aging.
... The secondary metabolites obtained from the cysteine accumulated in plants of the Allium genus are S-alqu(en)yl-cysteine sulfoxides; alliin, which transforms into allicin; N-acetylcysteine; S-allylcysteine; and S-allyl-mercapto cysteine [80,81]. These active principles have antioxidant, anti-inflammatory, and anticancer properties [82]. ...
... It is also garlic's most important active component, with antiseptic, antiviral, antifungal, antiparasitic, and antibacterial properties [63,84]. In addition, allicin and ajoene are the active components used in veterinary medicine and livestock production [85,86], and their benefits and antiparasitic properties on the zootechnical performance of farm animals have been reported [63, [78][79][80][81][82][83][84][85][86][87][88]. ...
How to cite this article: Delgado DLC, Caceres LLC, Gómez SAC, and Odio AD (2023) Effect of dietary garlic (Allium sativum) on the zootechnical performance and health indicators of aquatic animals: A mini-review, Veterinary World, 16(5): 965-976. Abstract Considerable efforts have been made by modern aquaculture to mitigate the environmental damages caused by its practices while also attempting to improve the quality of the aquatic organisms by promoting alternatives, such as the use of natural products, like garlic (Allium sativum), and instead of chemical agents. Garlic has multiple properties, including antifungal, antibacterial, antiviral, antitoxic, and anticancer effects. In fish, the antiparasitic activity of garlic is one of the most reported effects in the literature, mainly using immersion baths for aquatic organisms. Using garlic also has an antimicrobial effect on the culture of aquatic organisms. Therefore, this review focuses on the impact of garlic on the health and production of aquatic organisms.
... The pathophysiological significance of endogenously produced H 2 S in various neurological models was investigated. Emerging preclinical evidence has shown that low concentrations of H 2 S shed light on the neuroprotective and neuromodulatory role during cognitive decline and brain injury (13,14). ...
Introduction: Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are known as gaseous autocoids. It is not clear how the application of exogenous NO, H2S and CO alters the thiol/disulfide balance and advanced oxidation protein products (AOPPs) in the hippocampus and serum. Materials and Methods: In the study, rats were exogenously injected with L-arginine (100 mg/kg) as a NO donor, NaHS (10 mg/ kg) as a H2S donor, and CORM-2 (10 mg/kg) as a CO donor (II) (a tricarbonyldichlororuthenium dimer). Thiol/disulfide balance and advanced protein oxidation products were analyzed in hippocampus and serum samples. Results: The native thiol level in the hippocampus of the L-arginine group was statistically decreased compared to the native thiol level of the control group (p≤0.0001). The disulfide level in the hippocampus of the L-arginine group was statistically increased compared to the control group (p=0.009). Hippocampal total thiol level of NaHS group and CORM-2 group increased statistically (p=0.008,p=0.0157, respectively), while serum disulfide level of CORM-2 group decreased (p=0.0005). Serum and hippocampus AOPPs levels of the NaHS group were statistically increased compared to the control group (***p=0.0006, **p=0.0047, respectively). Similarly, the hippocampal AOPP level in the CORM-2 group was found to be statistically increased compared to the AOPP level in the control group (p=0.0437). Conclusion: As NaHS can improve thiol/disulfide balance, new studies are needed for CORM-2 and L-Arginine. This study is the first to report the effects of NO, H2S and CO on thiol/disulfide balance and AOPPs in the hippocampus and serum. Keywords: NO, H2S, CO, AOPPs, Thiol/disulfide
... H 2 S also promotes endothelial cell proliferation and angiogenesis [15,16], thus enhancing tissue regeneration. In addition, H 2 S shows complex effects in inflammation [17] and cancers [2], and involves in some diseases such as Alzheimer's disease [18], Parkinson's disease [19] and glycometabolic disorders [20]. It should be noted that H 2 S follows dose-dependent biological effects. ...
Hydrogen sulfide (H2S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H2S are highly associated with its concentrations. At relatively low concentration, H2S shows beneficial functions. However, long-time and high-dose donation of H2S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H2S delivery for precision medicine, H2S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H2S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H2S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H2S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H2S therapies especially imaging-guided H2S theranostics are highlighted. Since H2S donors with stimuli-responsive characters are vital components for establishing intelligent H2S delivery systems, the development of H2S donors is also briefly introduced.
... Hydrogen sulfide (H2S) is considered the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). The mammalian brain produces H2S abundantly through four enzymatic pathways, ensuring its redundancy in the organ (Cao et al., 2018). Currently, it is considered an emerging neuroprotectant as well as a neuromodulator (Panthi et al., 2018). ...
... Despite the fact that the role of endogenous H2S is still unclear in the pathophysiology of PD yet various researches have revealed that exogenous H2S has been shown to be protective against it.H2S has been proved to protect against neuronal loss in a number of PD models, pointing out that this gaseous molecule may be a new hope for this devastating disease. Recent studies have found that H2S protective effects are attributed to its anti-oxidant, antiinflammatory, anti-apoptotic and prosurvival activity (Cao et al., 2018). ...
... Regarding H2S's protective role, numerous in vitro and in vivo PD models have shown it to be effective, indicating that it may offer new hope for the treatment of PD. Studies have demonstrated that the antioxidation, anti-inflammation, anti-apoptosis, and pro-survival activity mediated by H2S are responsible for its protective effect (Cao et al., 2018). stated that H2S's protective effect is mediated via the negative regulation of epigenetic histone acetylation in Parkinson's disease. ...
Background: Parkinson's disease (PD) is the most common age-related motor neurodegenerative disease. Current therapeutic modalities for PD are directed at controlling the motor symptoms to slow disease progression, while no exact therapy exists to repair the immient neuronal damage. Despite the involvement of exosomes in the pathogenesis of PD, they serve as a promising therapeutic tool. Exosomes can restore the homeostasis of oxidative stress, neuro-inflammation, and cell apoptosis. Although H2S is involved in the pathogenesis of PD, it has anti-oxidant, anti-inflammatory and anti-apoptotic neuroprotective effects, giving hope for the role of this gaseous molecule in PD therapy. Objective: We aimed to evaluate the therapeutic effect of exosomes and/ or H2S-donor (NaHS) on PD, through modulation of PI3K/AKT signaling pathway, and to compare their combined effect with the standard treatment, L-DOPA. Methods: This study was conducted on forty-eight female white albino rats divided equally into 6 groups: control group, Parkinson group induced by 6-hydroxydopamine (6-OHDA), 3 Parkinson groups treated with either L-DOPA, exosomes, or H2S-donor (NaHS), and Parkinson group treated with both exosomes and NaHS. The following parameters were assessed in the rat brain tissues: gene expression of Nrf2, Keap1, α-synuclein, and miRNA-141, protein levels of PI3K, AKT, Dopamine, TNF-α and caspase-3. GSH and MDA levels were also measured. In addition, behavioral function tests and histo-pathological examination of rat brain tissues were also performed. Results: In the Parkinson group, there was a significant deficit in behavioral functions, along with down-regulation of the Nrf2 gene and its downstream antioxidant GSH, and increased levels of the lipid peroxidation biomarker MDA. Also, there was increased neuro-inflammation as evidenced by increased levels of TNF-α with decreased levels of the neurotransmitter Dopamine. Moreover, there was increased gene expression of Keap-1, miRNA-141, and α-synuclein associated with decreased levels of AKT, PI3K and increased caspase-3 levels. On the other hand, all treated groups, especially the combined exosomes and H2S donor-treated group, significantly reversed the deteriorating impacts of 6-OHDA on rat brains, as evidenced by the improvement of the behavioral dysfunction and the histopathological picture, which agrees with the biochemical and molecular findings of PI3K/AKT signaling pathway. Conclusion: These data suggest that combined exosomes and H2S-donor could be considered as a potential and effective line for treating PD.
