The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway.

Abstract

Hepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury. Two doses of shikonin (7.5 and 12.5 mg/kg) were administered 2 h before surgery. Balb/c mice were randomly divided into four groups: normal control, I/R, and shikonin preconditioning at two doses (7.5 and 12.5 mg/kg). The serum and liver tissues were collected at three time points (3, 6, and 24 h). Shikonin significantly reduced serum AST and ALT levels and improved pathological features. Shikonin affected the expression of Bcl-2, Bax, caspase 3, caspase 9, Beclin-1, and LC3, and upregulated PI3K and p-Akt compared with the levels in the I/R group. Shikonin attenuated hepatic I/R injury by inhibiting apoptosis and autophagy through a mechanism involving the activation of PI3K/Akt signaling.

• Authors: Tong Liu, QingHui Zhang, Wenhui Mo, Qiang Yu, Shizan Xu, Jingjing Li, Sainan Li, Jiao Feng, Liwei Wu, Xiya Lu, Rong Zhang, Linqiang Li, Keran Cheng, Yuqing Zhou, Shunfeng Zhou, Rui Kong, Fan Wang, Weiqi Dai, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Yan Zhao, Chuanyong Guo
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 44785 (03 21 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28322249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Inflammation Mediators
• Naphthoquinones
• Protective Agents
• shikonin
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Dimethyl Sulfoxide

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cytokines (metabolism)
• Dimethyl Sulfoxide
• Enzyme Activation (drug effects)
• Hepatocytes (drug effects, metabolism, pathology)
• Inflammation Mediators (metabolism)
• Liver (drug effects, pathology, physiopathology, ultrastructure)
• Liver Function Tests
• Male
• Mice, Inbred BALB C
• Models, Biological
• Naphthoquinones (pharmacology, therapeutic use)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protective Agents (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reperfusion Injury (drug therapy, enzymology, pathology, physiopathology)
• Signal Transduction