L-carnitine alleviates liver warm ischemia-reperfusion injury in rats through activating Nrf2/HO-1 pathway

Abstract

Objective To investigate the protective effects of L-carnitine on liver warm ischemia-reperfusion injury (WIRI) in rats and to explore its possible role of L-carnitine in affecting Nrf2/HO-1 pathway. Methods Twenty-four male Sprague-Dawley (SD) rats were randomly divided into three groups including sham-operated (SO) group, liver warm ischemia and reperfusion (WIR) group and L-carnitine pretreatment (LC) group. L-carnitine was injected intraperitoneally in LC group while the equal volume of saline was injected in SO group and WIR group. The levels of ALT and AST in serum as well as the activities of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in liver tissues were detected. Meanwhile, pathologic change of liver tissue was observed. And then, the mRNA expression of NF-E2-related factor 2(Nrf2) and heme oxygenase 1(HO-1) in liver tissues was determined. Results Compared with the SO group, ALT and AST level in serum were significantly increased (P<0.05) in the WIR group; the activity of SOD in liver tissues was significantly reduced in the WIR group [(66.6±12.3) U/mgprot vs. (25.1±9.0) U/mgprot, P<0.05]; and the content of MDA in liver tissues was significantly increased in the WIR group [(1.5±0.3) nmol/mgprot vs. (3.6±0.8) nmol/mgprot, P<0.05]; the mRNA expression of Nrf2 and HO-1 were significantly increased (P<0.05) in the WIR group. Compared with the WIR group, ALT and AST level in serum were significantly reduced (P<0.05) in the LC group; the activity of SOD in liver tissues was significantly increased in the LC group [(25.1±9.0) U/mgprot vs. (86.0±11.4) U/mgprot, P<0.05)]; and the content of MDA in liver tissues was significantly reduced in the LC group [(3.6±0.8) nmol/mgprot vs. (1.4±0.2)nmol/mgprot, P<0.05]; the mRNA expression of Nrf2 and HO-1 were significantly increased (P<0.05) in the LC group. Conclusion L-carnitine may attenuate liver WIRI in rats, and this protective effect may be through activating the Nrf2/HO-1 pathway. Key words: L-Carnitine; Liver warm ischemia-reperfusion injury; Nrf2; HO-1; Oxidative stress