Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. May 14, 2008; 14(18): 2832-2837
Published online May 14, 2008. doi: 10.3748/wjg.14.2832
Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice
Ping-Guo Liu, Song-Qing He, Yan-Hong Zhang, Jian Wu
Ping-Guo Liu, Song-Qing He, Yan-Hong Zhang, Jian Wu, Department of Internal Medicine, Transplant Research Program, University of California, Davis Medical Center, Sacramento, CA 95817, United States
Ping-Guo Liu, Department of Hepatic-Biliary Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361004, Fujian Province, China
Author contributions: Liu PG designed and performed the most of the study; He SQ contributed to an initial idea and helped with MCLA measurement; Zhang YH helped with apoptosis staining; Wu J is the principal investigator, conducted data analysis and manuscript preparation.
Correspondence to: Jian Wu, MD, PhD, UC Davis Medical Center, Transplant Research Institute, 4635 2nd Ave. Suite 1001, Sacramento, CA 95817, United States. jdwu@ucdavis.edu
Telephone: +1-916-7348044
Fax: +1-916-7348097
Received: March 10, 2008
Revised: March 27, 2008
Published online: May 14, 2008
Abstract

AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice.

METHODS: Mice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX) inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion.

RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-α levels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure.

CONCLUSION: Allopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generation of superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.

Keywords: Ischemia/reperfusion; Reactive oxygen species; Allopurinol; Apocynin; NADPH oxidase; Xanthine oxidase