Protective effects of melatonin and N-acetylcysteine on hepatic injury in a rat cardiopulmonary bypass model

Background. An increasing number of patients were undergoing cardiac surgery with cardiopulmonary bypass (CPB) and more attention had been paid to hepatic injury after CPB. This study was designed to test the hypothesis that melatonin and N-acetylcysteine (NAC) could attenuate hepatic injury induced by CPB in rats. Materials and methods. Male Sprague Dawley rats were randomly divided into four groups: sham, control (CPB + placebo), NAC (CPB + 250 mg/kg N-acetylcysteine), and melatonin (CPB + 20 mg/kg melatonin). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2, 3, and 24 h postoperation. Liver samples were harvested at 24 h after the operation. Results. In the control group, the levels of serum liver enzymes and tumor necrosis factor-a, activities of inducible nitric oxide synthase, malondialdehyde, and myelo-peroxidase in liver tissue were significantly increased. In addition, swollen hepatocytes, vacuolization, and congestion in sinusoids were observed. These changes were markedly reversed in both NAC and melatonin groups. Furthermore, the glutathione content and liver antioxidative enzymes activities were significantly decreased in the control group compared with the sham group. However, the levels of these antioxidants were markedly elevated after NAC or melatonin treatment compared with placebo treatment. Conclusions. Our findings showed that NAC and melatonin had acceptably beneficial effects against the CPB-induced hepatic injury. (c) 2007 Elsevier Inc. All rights reserved.