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: Jun Yin, Chao Tu, Jie Zhao, Danmin Ou, Guangwen Chen, Ying Liu, Xianzhong Xiao
• Journal: Brain research (Brain Res) Vol. 1491 Pg. 188-96 (Jan 23 2013) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 23123706 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Biomarkers
• Neuroprotective Agents
• Malondialdehyde
• Superoxide Dismutase
• Hydrogen Sulfide

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Apoptosis (drug effects)
• Biomarkers (blood)
• Blotting, Western
• Brain Ischemia (pathology, prevention & control)
• Cerebral Infarction (pathology)
• Enzyme-Linked Immunosorbent Assay
• Hydrogen Sulfide (pharmacology)
• Inflammation (metabolism, prevention & control)
• Male
• Malondialdehyde (metabolism)
• Neuroprotective Agents
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Reperfusion Injury (pathology, prevention & control)
• Signal Transduction (drug effects)
• Stroke
• Superoxide Dismutase (metabolism)