Hydrogen sulfide ameliorates ischemia/reperfusion-induced hepatitis by inhibiting apoptosis and autophagy pathways.

Abstract

BACKGROUND:

Hepatic ischemia/reperfusion (I/R) injury is an important clinical problem, and its consequences can seriously threaten human health. Apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule and is known to exert a protective effect against hepatic I/R injury. In this study, the purpose is to explore both the effect and mechanism of H2S on hepatic I/R injury.

METHODS:

Balb/c mice were randomized into Sham, I/R, or two doses (14 μmol/kg and 28 μmol/kg) of sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups.

RESULTS:

NaHS significantly reduced the levels of TNF- α and IL-6 at 12 h and 24 h after injection compared with ischemia/reperfusion challenge alone. The expression of Bcl-2, Bax, Beclin-1, and LC3, which play important roles in the regulation of the apoptosis and autophagy pathways, was also clearly affected by NaHS. Furthermore, NaHS affected the p-JNK1, p-ERK1, and p-p38.

CONCLUSION:

Our results indicate that H2S attenuates hepatic I/R injury, at least in part, by regulating apoptosis through inhibiting JNK1 signaling. The autophagy agonist rapamycin potentiated this hepatoprotective effect by reversing the inhibition of autophagy by H2S.

• Authors: Ping Cheng, Fan Wang, Kan Chen, Miao Shen, Weiqi Dai, Ling Xu, Yan Zhang, Chengfen Wang, Jingjing Li, Jing Yang, Rong Zhu, Huawei Zhang, Yuanyuan Zheng, Jie Lu, Yingqun Zhou, Chuanyong Guo
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2014 Pg. 935251 ( 2014) ISSN: 1466-1861 [Electronic] United States
• PMID: 24966472 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Bax protein, mouse
• Beclin-1
• Becn1 protein, mouse
• Interleukin-6
• Map1lc3b protein, mouse
• Microtubule-Associated Proteins
• Proto-Oncogene Proteins c-bcl-2
• Sulfides
• Tumor Necrosis Factor-alpha
• bcl-2-Associated X Protein
• sodium bisulfide
• Hydrogen Sulfide

Topics

• Animals
• Apoptosis
• Apoptosis Regulatory Proteins (metabolism)
• Autophagy
• Beclin-1
• Hepatitis (drug therapy, physiopathology)
• Humans
• Hydrogen Sulfide (pharmacology)
• Interleukin-6 (metabolism)
• Liver (drug effects)
• Male
• Mice
• Mice, Inbred BALB C
• Microtubule-Associated Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Random Allocation
• Reperfusion Injury (pathology)
• Sulfides (pharmacology)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• bcl-2-Associated X Protein (metabolism)