title: Exogenous hydrogen sulfide protects against global cerebral ischemia/reperfusion injury via its anti-oxidative, anti-inflammatory and anti-apoptotic effects in rats.
abstract: The present study was undertaken to study the effects of exogenous hydrogen sulfide (H(2)S) on global cerebral ischemia-reperfusion(I/R) and the underlying mechanisms. After a 24h I/R, administration of NaHS, an exogenous donor for H(2)S, at the dose of 0.2 or 0.4 μmol/kg significantly decreased the apoplexy index, neurological symptom scoring, and brain infarcted area as compared to the I/R group in a dose dependent manner. At the same time, NaHS-treated rats displayed significant reduction of MDA content, and striking increase of SOD activity in the brain tissues compared with I/R group. The up-regulated mRNA levels of p47(phox) and gp91(phox) subunits of NADPH oxidase were also suppressed by NaHS treatment. In this study, the pro-inflammatory markers TNF-α and MCP-1 in I/R group were markedly increased by 24h I/R, which were significantly attenuated by NaHS in a dose-dependent manner. In contrast, the anti-inflammatory factor IL-10 was markedly induced by NaHS administration. In addition, the expression of the anti-apoptotic protein Bcl-2 was significantly decreased in I/R group compared with the sham-operated group. This reduction was significantly blunted in NaHS-treated group. On the contrary, the pro-apoptotic protein Bax content in brain tissues of I/R group was markedly elevated compared with sham-operated animals. And such an induction of Bax content was significantly ameliorated by NaHS. Taken together, our results suggest that hydrogen sulfide has potent protective effect against a severe cerebral injury induced by a global I/R possibly through the inhibition of oxidative stress, inflammation and apoptosis.
authors.affiliation: Clinical Medicine for Eight-year-program, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Chao
authors.initials: C
authors.lastname: Tu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Danmin
authors.initials: D
authors.lastname: Ou
authors.forename: Guangwen
authors.initials: G
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D006862:Hydrogen Sulfide