Hydrogen Sulfide Ameliorates Ischemia/Reperfusion-Induced Hepatitis by Inhibiting Apoptosis and Autophagy Pathways

• Published in: Mediators of Inflammation Vol. 2014; no. 9; pp. 345 - 360
• Main Authors: Li, Jingjing, Yang, Jing, Zhang, Huawei, Zheng, Yuanyuan, Lu, Jie, Zhou, Ying-Qun, Guo, Chuan-Yong, Wang, Chengfen, Zhang, Yan, Xu, Ling, Weiqi, Dai, Shen, Miao, Chen, Kan, Wang, Fan, Cheng, Ping, Zhu, Rong
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01.01.2014; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Autophagy; Autophagy (Cytology); bcl-2-Associated X Protein - metabolism; Beclin-1; Health aspects; Hepatitis; Hepatitis - drug therapy; Hepatitis - physiopathology; Humans; Hydrogen sulfide; Hydrogen Sulfide - pharmacology; Interleukin-6 - metabolism; Ischemia; 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
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2014/935251

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.