Effects of nitric oxide on hepatic dysfunction induced by thioacetaminde in rats

ＥｆｅｃｔｓｏｆｎｉｔｒｉｃｏｘｉｄｅｏｎｈｅｐａｔｉｃｄｙｓｆｕｎｃｔｉｏｎｉｎｄｕｃｅｄｂｙｔｈｉｏａｃｅｔａｍｉｎｄｅｉｎｒａｔｓＺｈｅｎｇＸｉａｏｂｉｎ郑晓宾，ＨａｎＤｅｗｕ韩德五，ＭａＸｕｅｈｕｉ马学惠，ＸｕＲｕｉｌｉｎｇ许瑞龄ａｎｄＺｈａ...

Effects of nitric oxide on hepatic dysfunction induced by thioacetaminde in rats

Objective To investigate the effects of nitric oxide (NO) on the hepatic dysfunction induced by thioacetaminde (TAA) in rats.Methods Wistar rats were randomly divided into four groups, namely Nω-Nitri-L-Arginine (NNA) group, TAA group, TAA+NNA group and normal control group. The rats in TAA group and TAA+NNA group were given TAA 300 mg/kg b.w. by gavage. After 24 h, rats in NNA and TAA+NNA groups received Nω-Nitri-L-Arginine (50 mg/kg) by intraperitoneal injection. Ten hours later all rats were killed. Endotoxin, lactate dehydrogenase (LDH), NO and creatinine contents in plasma and NO levels in brain tissue were determined. Electroencephalograms of the rats were recorded before they were killed.Results 1). The rats in TAA+NNA group were inactive, sleepy and their electroencephalograms presented δ waves, but only α and β waves were found in other three groups. It was indicated that hepatic encephalopathy might occur in the rats in TAA+NNA group. 2). Endotoxin contents in plasma were increased in the rats in TAA group and TAA+NNA group. It was shown that TAA induced gut-derived endotoxemia (normal control group 0.149±0.059 Eu/ml vs TAA group 0.222±0.117 Eu/ml, TAA+NNA group 0.235±0.52 Eu/ml, P<0.01). 3). NO production was enhanced in plasma and brain tissue of the rats treated with TAA, but NO production was significantly lower in TAA+NNA group than in TAA group (plasma: 41.59±2.75 μmol/L vs 51.63±3.81 μmol/L, P<0.01; brain tissue: 48.10±4.71 μmol/L vs 69.70±8.87 μmol/L, P<0.01). 4). LDH and creatinine levels in plasma were higher in TAA+NNA group than in TAA group (LDH: 854.83±87.48 U/L vs 570.72±116.74 U/L, P<0.01; creatinine: 361.04±153.68 μmol/L vs 153.40±28.90 μmol/L, P<0.01). 5). No changes were found in biochemistry test and electroencephalogram in NNA group.Conclusion The results showed that TAA could induce gut-derived endotoxemia in rats, and endotoxin could stimulate NO production in plasma and brain tissue. By inhibiting NO production with NNA, encephalopathy, dysfunction of liver and kidney occurred in rats of TAA+NNA group. It is suggested that NO might have protective effect in experimental hepatic dysfunction induced by TAA.