Clinical and Enzymatic Investigation of Induction of Oxygen Free Radicals by Ischemia and Reperfusion in Human Hepatocellular Carcinoma and Adjacent Liver

摘要

Serum concentration of thiobarbituric acid (TBA) reactants in the hepatic vein were measured beforeand after transient dearterialization of the liver in five human subjects bearing unresectablehepatocellular carcinoma (HCC). During 1 hour of the occlusion of the hepatic artery, change inTBAreactants level was slight. However, the mean value of TBA reactants in 1 hour after the reflowincreased to 1.50 ± 0.11 nmol/ml (mean ± S.E.) and was significantly higher (p < 0.05) than thosebefore 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 inhuman untreated HCC and the corresponding adjacent liver tissue. The results demonstrated anincrease in SOD in 81.8% (9/11) of HCC, and a decrease in CAT in 72.7% (8/11) of HCC whencompared with the corresponding adjacent liver tissue. The mean value of SOD in HCC wassignificantly higher (66.8 ± 6.5 vs 52.8 ± 3.8 U/mg protein; p < 0.05), and that of CAT wassignificantly lower (22.6 ± 2.4 vs 36.0 ± 6.1 U/mg protein; p < 0.05) than those in liver tissue. All ofnine HCC samples had a significantly lower activity of XOD (6.4 ± 1.9 vs 20.3 ± 3.4 pmol/minute/mgprotein; p < 0.01) than the corresponding liver tissue. There was no obvious relation between thecontent of SOD and CAT in HCC, or in liver tissue.These data may suggest that oxygen free radicals can be generated in human HCC by ischemiaand reperfusion of the tumor- bearing liver. It is also indicated that the antioxidant system of HCC isnot always impaired, and that HCC might develop several lines of defence systems against theoxidative attack. A possible strategy of the treatment for liver tumor with oxygen derived free radicalsinduced by ischemia and reperfusion is hypothized here.