A Study On The Protective Effect Of N-acetylcysteine On Acute Alcoholic Liver Injury In Rats

Objective:To investigate the protective effect of N-acetylcysteine(NAC) on acute alcoholic liver injury in rats.Methods:The liver injury rat models were induced by infusing alcohol into stomach of rats. Fifty male Wistar rats were randomly divided into 5 groups(n=10):control group, acute liver injury model group, and low-(150mg/kg), middle-(300mg/kg), high-(600mg/kg) dose group of N-acetylcysteine. The control group were given the same amount of salime instead of alcohol through intraperitpneal injection and gastric infusion. The model group were infused stomach with 56°liqueur once a day for 10d. Different doses of N-acetylcysteine groups were injected NAC intraperitoneally at 30 min before infusing liqueur once a day for 10d. After treatment, the liver indices were measured and aorta blood and liver tissue were collected. Serum was isolated for measurement of alanine transaminase(ALT), aspartate transaminase(AST) activity and tumor necrosis factor-a(TNF-a) content. Liver tissue homogenate was prepared to assay superoxide dismutase(SOD), glutathione perioxidase(GSH-Px) activities and malondialdehyde (MDA) content. The liver histopathologies were explored with HE staining. The expression of nuclear factor-kappa B(NF-κB) and Caspase-3 in liver were detected by immunohistochemistry.Results:①Compared with control group, liver indices, serum ALT, AST level and TNF-αcontent increased, liver tissue MDA content and the expression of NF-κB and Caspase-3 increased, SOD, GSH-Px activities decreased(P<0.01) significantly in model group. Under light microscope, the structure of the liver tissue was disorded, with a serious liver steatosis, accompanied by the infiltration of inflammatory cells.②After treatment, serum ALT, AST level and liver indices decreased, and liver tissues MDA content decreased, SOD, GSH-Px activities increased in difference doses of NAC groups(P<0.01 or P<0.05), the difference was significant compared with model group. Compared with low-dose group, MDA content decreased, SOD, GSH-Px activity increased in middle and high-dose groups(P<0.01 or P<0.05).Compared with the middle dose group, SOD activity was significantly higher in high-dose group(P<0.01).③Under light microscope, the treatment groups were lighter in liver steatosis and the degree of inflammation than the model group. High-dose group and control group were not significantly different. The middle-dose group had a slight steatosis and the low-dose group have a more serious steatosis.④In three different doses of NAC groups, the expression of NF-κB and Caspase-3 were significantly reduced, serum TNF-a content were decreased(P<0.01 or P<0.05). Compared with model group, the difference was significant. Compared with low-dose group, the expression of NF-κB and Caspase-3 reduced in middle and high-dose group, serum TNF-a decreased in the high-dose group(P<0.01 or P<0.05). Compared with the middle-dose group, the expression of NF-κB and Caspase-3 were reduced, serumTNF-a content decreased in the high-dose group(P<0.01 or P<0.05).Conclusions:The acute alcoholic liver injury models in rats were made successfully. N-acetylcysteine can not only reduce the lipid peroxidation product MDA content, but also improve the liver tissue antioxidant enzymes SOD, GSH-Px activity, to improve liver function, reduce the accumulation of lipid in liver cells. Also, it can reduce the release of inflammatory cytokines by inhibiting NF-κB activating, and inhibit apoptosis signal transduction, having anti-inflammatory and anti-apoptotic effects. Thus NAC might have effect of alleviating the liver injury induced by alcohol and its therapeutic effect has a certain dose-effect relationship.