thiobarbituric-acid and Carcinoma--Hepatocellular

N-nitrosodiethylamine (NDEA) is a potent carcinogenic agent that induces liver cancer. To evaluate the chemopreventive function of melatonin in this experimental model, Wistar male rats received a single i.p. injection of NDEA or vehicle followed by weekly s.c. injections of carbon tetrachloride or vehicle for 6 weeks. Melatonin (5 mg/kg body weight) or its vehicle (0.5 mL saline) was given i.p. on a daily basis 2 hr before lights off for 20 wk. At the end of this period the rats were killed and liver and blood samples were taken for histological and biochemical studies. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein were measured in serum. To assess lipid peroxidation and the antioxidant status in liver and blood, the levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was assessed in liver and erythrocyte fraction of NDEA-treated rats. NDEA administration inhibited body weight, macro- and microscopically detectable liver tumors and increased levels of plasma AST, ALT and alpha-fetoprotein. NDEA treatment decreased liver TBARS levels and CAT and SOD activities and increased liver GSH levels and GST and GPx activities. Plasma TBARS were augmented, while plasma GSH levels and the activities of erythrocyte CAT, SOD, GST and GPx decreased, in NDEA-treated rats. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diethylnitrosamine; Glutathione; Male; Melatonin; Rats; Rats, Wistar; Thiobarbiturates

Serum concentration of thiobarbituric acid (TBA) reactants in the hepatic vein were measured before and after transient dearterialization of the liver in five human subjects bearing unresectable hepatocellular carcinoma (HCC). During 1 hour of the occlusion of the hepatic artery, change in TBA reactants level was slight. However, the mean value of TBA reactants in 1 hour after the reflow increased to 1.50 +/- 0.11 nmol/ml (mean +/- S.E.) and was significantly higher (p < 0.05) than those before hepatic dearterialization (1.28 +/- 0.11 nmol/ml) and just before the release of occlusion (1.32 +/- 0.09 nmol/ml). Further, two endogeneous scavenger enzymes, superoxide dismutase (SOD) and catalase (CAT), and one of the major sources of oxygen free radicals, xanthine oxidase (XOD) were measured in human untreated HCC and the corresponding adjacent liver tissue. The results demonstrated an increase in SOD in 81.8% (9/11) of HCC, and a decrease in CAT in 72.7% (8/11) of HCC when compared with the corresponding adjacent liver tissue. The mean value of SOD in HCC was significantly higher (66.8 +/- 6.5 vs 52.8 +/- 3.8 U/mg protein; p < 0.05), and that of CAT was significantly lower (22.6 +/- 2.4 vs 36.0 +/- 6.1 U/mg protein; p < 0.05) than those in liver tissue. All of nine HCC samples had a significantly lower activity of XOD (6.4 +/- 1.9 vs 20.3 +/- 3.4 pmol/minute/mg protein; p < 0.01) than the corresponding liver tissue. There was no obvious relation between the content of SOD and CAT in HCC, or in liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Carcinoma, Hepatocellular; Catalase; Female; Free Radicals; Humans; Ischemia; Liver; Liver Circulation; Liver Neoplasms; Male; Middle Aged; Oxygen; Reactive Oxygen Species; Reperfusion; Superoxide Dismutase; Thiobarbiturates; Xanthine Oxidase