• Jianhua Rao, Xiaofeng Qian, Ping Wang, Liyong Pu, Yuan Zhai, Xuehao Wang, Feng Zhang, and Ling Lu.
• Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing 210029, China.
• J. Surg. Res. 2013 Apr 1; 180 (2): e99-e106.

BackgroundInflammatory response plays a pathogenic role in liver ischemia/reperfusion (I/R) injury. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A with anti-inflammatory effects. However, there are few reports on the anti-inflammatory effects of ATRA on liver I/R injury. The purpose of this study was to investigate the effects of ATRA on liver I/R injury and related mechanisms.MethodsA total of 54 male Sprague-Dawley rats were randomly divided into three groups (18 rats each), namely, sham, I/R, and I/R+ATRA groups. ATRA was intraperitoneally administered at a dose of 15mg/kg/d 14d before ischemia surgery. The segmental (70%) hepatic ischemia model was used by clamping the portal vein, hepatic artery, and bile duct of the left and median for 1h. The rats were sacrificed 3, 6, and 24h after reperfusion, and blood and liver tissue samples were obtained. Liver injury was evaluated by biochemical and histopathologic examinations. Myeloperoxidase activity was spectrophotometrically measured. The expression of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6 was measured by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Liver nuclear factor kappa B (NF-κB) was detected by immunohistochemistry. The expression of NF-κB p65 and inhibitor NF-κB-α (IκBα) was determined by Western blot analysis.ResultsThe serum alanine aminotransferase level, Suzuki scores of hepatic histology, and hepatic myeloperoxidase activity, as indices of hepatic injury, were increased after reperfusion. The increase was attenuated by preadministration with ATRA. Compared with the I/R group, ATRA treatment increased IκBα expression and suppressed NF-κB p65 expression. Subsequently, the levels of tumor necrosis factor-α and interleukin-6 after liver I/R were effectively downregulated.ConclusionsATRA administration can significantly attenuate I/R injury in rat liver. The protective mechanism is related to its anti-inflammatory function of inhibiting NF-κB activation.Copyright © 2013 Elsevier Inc. All rights reserved.

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