scholarly journals Hydrogen Sulfide Ameliorates Developmental Impairments of Rat Offspring with Prenatal Hyperhomocysteinemia

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
O. V. Yakovleva ◽  
A. R. Ziganshina ◽  
S. A. Dmitrieva ◽  
A. N. Arslanova ◽  
A. V. Yakovlev ◽  
...  

Maternal high levels of the redox active amino acid homocysteine—called hyperhomocysteinemia (hHCY)—can affect the health state of the progeny. The effects of hydrogen sulfide (H2S) treatment on rats with maternal hHCY remain unknown. In the present study, we characterized the physical development, reflex ontogeny, locomotion and exploratory activity, muscle strength, motor coordination, and brain redox state of pups with maternal hHCY and tested potential beneficial action of the H2S donor—sodium hydrosulfide (NaHS)—on these parameters. Our results indicate a significant decrease in litter size and body weight of pups from dams fed with methionine-rich diet. In hHCY pups, a delay in the formation of sensory-motor reflexes was observed. Locomotor activity tested in the open field by head rearings, crossed squares, and rearings of hHCY pups at all studied ages (P8, P16, and P26) was diminished. Exploratory activity was decreased, and emotionality was higher in rats with hHCY. Prenatal hHCY resulted in reduced muscle strength and motor coordination assessed by the paw grip endurance test and rotarod test. Remarkably, administration of NaHS to pregnant rats with hHCY prevented the observed deleterious effects of high homocysteine on fetus development. In rats with prenatal hHCY, the endogenous generation of H2S brain tissues was lower compared to control and NaHS administration restored the H2S level to control values. Moreover, using redox signaling assays, we found an increased level of malondialdehyde (MDA), the end product of lipid peroxidation, and decreased activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the brain tissues of rats of the hHCY group. Notably, NaHS treatment restored the level of MDA and the activity of SOD and GPx. Our data suggest that H2S has neuroprotective/antioxidant effects against homocysteine-induced neurotoxicity providing a potential strategy for the prevention of developmental impairments in newborns.

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 995 ◽  
Author(s):  
Olga Yakovleva ◽  
Ksenia Bogatova ◽  
Renata Mukhtarova ◽  
Aleksey Yakovlev ◽  
Viktoria Shakhmatova ◽  
...  

Hydrogen sulfide (H2S) is endogenously produced from sulfur containing amino acids, including homocysteine and exerts neuroprotective effects. An increase of homocysteine during pregnancy impairs fetal growth and development of the offspring due to severe oxidative stress. We analyzed the effects of the H2S donor—sodium hydrosulfide (NaHS) administered to female rats with hyperhomocysteinemia (hHcy) on behavioral impairments and levels of oxidative stress of their offspring. Rats born from females fed with control or high methionine diet, with or without H2S donor injections were investigated. Rats with maternal hHcy exhibit increased levels of total locomotor activity and anxiety, decreased muscle endurance and motor coordination, abnormalities of fine motor control, as well as reduced spatial memory and learning. Oxidative stress in brain tissues measured by activity of glutathione peroxidases and the level of malondialdehyde was higher in rats with maternal hHcy. Concentrations of H2S and the activity and expression of the H2S generating enzyme—cystathionine-beta synthase—were lower compared to the control group. Administration of the H2S donor to females with hHcy during pregnancy prevented behavioral alterations and oxidative stress of their offspring. The acquisition of behavioral together with biochemical studies will add to our knowledge about homocysteine neurotoxicity and proposes H2S as a potential agent for therapy of hHcy associated disorders.


2015 ◽  
Vol 309 (11) ◽  
pp. E925-E935 ◽  
Author(s):  
Li Sun ◽  
Song Zhang ◽  
Chengyuan Yu ◽  
Zhenwei Pan ◽  
Yang Liu ◽  
...  

Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2−/− mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway.


Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 603
Author(s):  
Cengiz Kaya ◽  
Bernardo Murillo-Amador ◽  
Muhammad Ashraf

The aim of this study is to assess the role of l-cysteine desulfhydrase (l-DES) and endogenous hydrogen sulfide (H2S) in glutathione (GSH)-induced tolerance to salinity stress (SS) in sweet pepper (Capsicum annuum L.). Two weeks after germination, before initiating SS, half of the pepper seedlings were retained for 12 h in a liquid solution containing H2S scavenger, hypotaurine (HT), or the l-DES inhibitor dl-propargylglycine (PAG). The seedlings were then exposed for three weeks to control or SS (100 mmol L−1 NaCl) and supplemented with or without GSH or GSH+NaHS (sodium hydrosulfide, H2S donor). Salinity suppressed dry biomass, leaf water potential, chlorophyll contents, maximum quantum efficiency, ascorbate, and the activities of dehydroascorbate reductase, monodehydroascorbate reductase, and glyoxalase II in plants. Contrarily, it enhanced the accumulation of hydrogen peroxide, malondialdehyde, methylglyoxal, electrolyte leakage, proline, GSH, the activities of glutathione reductase, peroxidase, catalase, superoxide dismutase, ascorbate peroxidase, glyoxalase I, and l-DES, as well as endogenous H2S content. Salinity enhanced leaf Na+ but reduced K+; however, the reverse was true with GSH application. Overall, the treatments, GSH and GSH+NaHS, effectively reversed the oxidative stress and upregulated salt tolerance in pepper plants by controlling the activities of the AsA-GSH and glyoxalase-system-related enzymes as well as the levels of osmolytes.


2020 ◽  
Vol 11 ◽  
Author(s):  
Longna Li ◽  
Yuhao Liu ◽  
Shu Wang ◽  
Jianxin Zou ◽  
Wenjiang Ding ◽  
...  

Magnesium hydride (MgH2) is a promising solid-state hydrogen source with high storage capacity (7.6 wt%). Although it is recently established that MgH2 has potential applications in medicine because it sustainably supplies hydrogen gas (H2), the biological functions of MgH2 in plants have not been observed yet. Also, the slow reaction kinetics restricts its practical applications. In this report, MgH2 (98% purity; 0.5–25 μm size) was firstly used as a hydrogen generation source for postharvest preservation of flowers. Compared with the direct hydrolysis of MgH2 in water, the efficiency of hydrogen production from MgH2 hydrolysis could be greatly improved when the citrate buffer solution is introduced. These results were further confirmed in the flower vase experiment by showing higher efficiency in increasing the production and the residence time of H2 in solution, compared with hydrogen-rich water. Mimicking the response of hydrogen-rich water and sodium hydrosulfide (a hydrogen sulfide donor), subsequent experiments discovered that MgH2-citrate buffer solution not only stimulated hydrogen sulfide (H2S) synthesis but also significantly prolonged the vase life of cut carnation flowers. Meanwhile, redox homeostasis was reestablished, and the increased transcripts of representative senescence-associated genes, including DcbGal and DcGST1, were partly abolished. By contrast, the discussed responses were obviously blocked by the inhibition of endogenous H2S with hypotaurine, an H2S scavenger. These results clearly revealed that MgH2-supplying H2 could prolong the vase life of cut carnation flowers via H2S signaling, and our results, therefore, open a new window for the possible application of hydrogen-releasing materials in agriculture.


2019 ◽  
Vol 97 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Kürşad Aytekin ◽  
Selma Şengiz Erhan ◽  
Züleyha Erişgin ◽  
Cem Zeki Esenyel ◽  
Selçuk Takır

Hydrogen sulfide (H2S) is found in both the plasma and synovial fluid of patients with gonarthrosis. In the present study, we investigated whether intra-articular injection of sodium hydrosulfide (NaSH) (1 mM, 30 μL), a H2S donor, might affect gonarthrosis in rats. Gonarthrosis was induced surgically in the left knees of rats and left for 6 weeks for the development of disease. Then, intra-articular injections of NaSH or methylprednisolone (1 mg/kg, 30 μL) were administered to rats. Half of each group was sacrificed at the end of the first day and the other half was sacrificed at the end of 4 weeks to evaluate early and later effects of injections on gonarthrosis. The injury induced by anterior cruciate ligament resection and medial meniscectomy in rats caused the development of gonarthrosis. As the duration lengthened after gonarthrosis induction, the progression of the disease continued. According to the modified Mankin Scoring System, intra-articular injection of NaSH histopathologically slowed the progression of gonarthrosis, whereas methylprednisolone was ineffective. In addition, NaSH decreased apoptosis in rat knees with gonarthrosis. Each treatment did not cause injury to healthy knees. Our results lead to the consideration that intra-articular NaSH administration may be effective in the progression of gonarthrosis.


2016 ◽  
Vol 310 (1) ◽  
pp. H71-H79 ◽  
Author(s):  
Maggie M. Kuo ◽  
Dae Hee Kim ◽  
Sandeep Jandu ◽  
Yehudit Bergman ◽  
Siqi Tan ◽  
...  

Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-γ-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, the MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be nitric oxide (NO) dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP and NaHS induced an increase in preconstriction tone, suggesting that endothelial NO synthase activity was not significantly inhibited. In vitro, H2S reacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S-based therapy in healthy and diseased coronary arteries.


2019 ◽  
Vol 47 (8) ◽  
pp. 3778-3791 ◽  
Author(s):  
Chao Yuan ◽  
Hai-Tao Hou ◽  
Huan-Xin Chen ◽  
Jun Wang ◽  
Zheng-Qing Wang ◽  
...  

Objective To investigate the role of hydrogen sulfide (H2S) in human internal mammary arteries (IMA) and its interaction with endothelial nitric oxide synthase (eNOS) and phosphodiesterase (PDE)5A activity. Methods Human IMA segments from patients undergoing coronary artery bypass grafting (CABG) were studied by myography for acetylcholine and sodium hydrosulfide (NaHS)-induced relaxation. Locations of 3-mercaptopyruvate sulfurtransferase (3-MPST) and cysteine aminotransferase (CAT) were examined immunohistochemically. Levels of H2S, eNOS, phosphorylated-eNOSser1177, and PDE5A were measured. Results In IMA segments from 47 patients, acetylcholine-induced relaxation (resistant to NG-nitro-L-arginine and indomethacin) was significantly attenuated by aminooxyacetic acid or L-aspartate (CAT inhibitors), iberiotoxin (large-conductance calcium-activated K+ channel blocker), TRAM-34 plus apamin (intermediate- and small-conductance Ca2+-activated K+ channel blockers) or glibenclamide (ATP-sensitive K+ channel blocker). 3-MPST and mitochondrial CAT were found in endothelial and smooth muscle cells while cytosolic CAT was located only in endothelial cells. Acetylcholine significantly increased the H2S levels. The H2S donor, NaHS, increased eNOS phosphorylation and down-regulated PDE5A. Conclusions Human conduit artery endothelium releases H2S under basal and stimulated conditions, involving the 3-MPST/CAT pathway, eNOS phosphorylation, PDE5A activity, and potassium channels. These findings may provide new therapeutic targets for treating vasospasm in CABG grafts and facilitate the development of new vasodilator drugs.


Author(s):  
Andrey P. Popov ◽  
Valentina I. Syutina

Due to the high frequency of strokes in the Russian Federation, leading to disability, loss of efficiency and loss of household autonomy, the development of methods of patients rehabilitation who have suffered acute cerebral circulation disorder is of high importance. The consequences of this condition is characterized by a number of syndromes, among which the leading role in reducing the motor activity of patients and limiting their ability to self-service, is hemiparesis, accompanied by a decrease in voluntary muscle strength in the affected limbs. We present the study results of computer stabilometry indicators as a means of assessing the ability to maintain static equilibrium in a standing position and control the oscillations of the general center of mass. We also present the evaluation results of arbitrary muscle strength of the affected limbs in patients with the consequences of acute cerebral circulation defect in the early recovery period. These studies were carried out as part of an experiment to assess the effectiveness of the multisensory stimulation technique, which is based on the combination of a number of stimulating and corrective effects in combination with physical exercises in closed and open kinematic circuits. The results of the study confirm the effectiveness of the developed method of physical rehabilitation.


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