Original Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Jun 28, 2010; 16(24): 3002-3010
Published online Jun 28, 2010. doi: 10.3748/wjg.v16.i24.3002
Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway
Xiao-Feng Tian, Ji-Hong Yao, Ling-Fei Ma, Hui-Rong Jing, Ying-Hua Li, Yu-Bing Li, Gang Shen, Feng Zhang, Hai-Dong Zhao
Hai-Dong Zhao, Feng Zhang, Gang Shen, Ying-Hua Li, Hui-Rong Jing, Ling-Fei Ma, Xiao-Feng Tian, Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
Yu-Bing Li, Ji-Hong Yao, Department of Pharmacology, Dalian Medical University, Dalian 116044, Liaoning Province, China
Author contributions: Tian XF, Yao JH and Zhao HD designed the research; Zhao HD, Zhang F, Shen G, Li YB and Li YH performed the research; Ma LF, Jing HR and Zhao HD analyzed the data; Zhao HD, Yao JH and Tian XF wrote the paper.
Supported by The grants of Chinese National Natural Science Foundation, No. 30872449; and the grants of the Dalian Scientific Research Foundation, No. 2008E13SF217
Correspondence to: Xiao-Feng Tian, Professor, Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China. txfdl@hotmail.com
Telephone: +86-411-84690722 Fax: +86-411-84672130
Received: March 20, 2010
Revised: April 18, 2010
Accepted: April 25, 2010
Published online: June 28, 2010
Abstract

AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antioxidant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R).

METHODS: Rats were divided randomly into four experimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfusion. In the SFN pretreatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg SFN 1 h before the operation. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Liver tissue superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were assayed. The liver transcription factor Nrf2 and heme oxygenase-1 (HO-1) were determined by immunohistochemical analysis and Western blotting analysis.

RESULTS: Intestinal I/R induced intestinal and liver injury, characterized by histological changes as well as a significant increase in serum AST and ALT levels (AST: 260.13 ± 40.17 U/L vs 186.00 ± 24.21 U/L, P < 0.01; ALT: 139.63 ± 11.35 U/L vs 48.38 ± 10.73 U/L, P < 0.01), all of which were reduced by pretreatment with SFN, respectively (AST: 260.13 ± 40.17 U/L vs 216.63 ± 22.65 U/L, P < 0.05; ALT: 139.63 ± 11.35 U/L vs 97.63 ± 15.56 U/L, P < 0.01). The activity of SOD in the liver tissue decreased after intestinal I/R (P < 0.01), which was enhanced by SFN pretreatment (P < 0.05). In addition, compared with the control group, SFN markedly reduced liver tissue MPO activity (P < 0.05) and elevated liver tissue GSH and GSH-Px activity (P < 0.05, P < 0.05), which was in parallel with the increased level of liver Nrf2 and HO-1 expression.

CONCLUSION: SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway.

Keywords: Sulforaphane, Liver injury, Intestinal ischemia reperfusion, NF-E2-related factor-2, Antioxidant response element