2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced lipid peroxidation in hepatic and extrahepatic tissues of male and female rats.

Abstract

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)2 administration to rats on lipid peroxidation (microsomal malondialdehyde formation and hepatic malondialdehyde content) was determined by the thiobarbituric acid method. The results demonstrate that dose and time-dependent lipid peroxidation occurs in hepatic as well as extrahepatic tissues. A 3–4 fold increase in hepatic lipid peroxidation was observed following the oral administration of TCDD. Lipid peroxidation also increases in other tissues as kidney and thymus, which are target tissues of TCDD. Sex differences exist with respect to the induction of lipid peroxidation by TCDD. A greater and more rapid induction of hepatic malondialdehyde (MDA) formation in response to TCDD is observed in female rats. When using arachidonic acid as an oxidizable substrate, more MDA was formed with hepatic, kidney and testes microsomes from TCDD-treated rats as compared to microsomes from control animals. No difference was found in the iron content of whole liver following TCDD administration. However, a 47% increase occurred in hepatic mitochondrial iron content, while a 52% decrease was observed in microsomal iron content per mg protein. The addition of ferrous ion to microsomes from control and treated animals resulted in a proportionally greater increase in MDA formation by control microsomes. Desferrioxamine addition to microsomes from control and TCDD-treated rats resulted in a decrease in MDA formation to the same basal level. The increase in MDA production by microsomes from TCDD-treated rats may be due, in part, to an increase in free ferrous ion.