AMELIORATIVE EFFECT OF DIETARY PROBUCOL ON POLYCHLORINATED BIPHENYLS-INDUCED HYPERCHOLESTEROLEMIA AND LIPID-PEROXIDATION IN THE RAT

The hypocholesterolemic and antioxidant activities of probucol (PB) we re examined in rats which were fed for 10 days with diets supplemented with or without 0.02% polychlorinated biphenyls (PCB). Dietary intake of PCB caused multiple effects on lipid metabolism, such as increased levels of both serum and HDL cholesterol, and increased TBA-reactive substances (TBARS), in hepatic subcellular fractions. PB 1% in compari son with either control or alpha-tocopherol (Toc) 0.1%, reduced the se rum cholesterol levels in normolipemic as well as in PCB-induced hyper cholesterolemic rats. In addition, this drug ameliorated the elevated TBARS induced by PCB in the hepatic subcellular fractions, although le ss antioxidant activity was noted in rats fed PB than in those fed Toc . The microsomes isolated from various groups were incubated for 2h at 37 degrees C in the presence or the absence of ferrous iron in vitro; microsomes from the PB-fed rats were as much resistant against lipid peroxidation in ferrous-free incubation medium as were those from Toc- fed rats, while in the presence of ferrous iron there was a higher ant ioxidant effect on lipid peroxidation in the latter fraction than in t he former. HPLC analyses showed that less PB than Toc was incorporated into the hepatic subcellular fractions, suggesting that the concentra tion of antioxidants in hepatic subcellular fractions determine the ex tent of lipid peroxidation in situ. These results suggest that the adm inistration of PB is an effective approach for the treatment of both h ypercholesterolemia and elevated lipid peroxidation while Toc ameliora tes only an elevated lipid peroxidation.