Ameliorative effect of dietary probucol on polychlorinated biphenyls-induced hypercholesterolemia and lipid peroxidation in the rat.
The hypocholesterolemic and antioxidant activities of probucol (PB) were 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 comparison with either control or alpha-tocopherol (Toc) 0.1%, reduced the serum cholesterol levels in normolipemic as well as in PCB-induced hypercholesterolemic rats. In addition, this drug ameliorated the elevated TBARS induced by PCB in the hepatic subcellular fractions, although less 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 antioxidant effect on lipid peroxidation in the latter fraction than in the former. HPLC analyses showed that less PB than Toc was incorporated into the hepatic subcellular fractions, suggesting that the concentration of antioxidants in hepatic subcellular fractions determine the extent of lipid peroxidation in situ. These results suggest that the administration of PB is an effective approach for the treatment of both hypercholesterolemia and elevated lipid peroxidation while Toc ameliorates only an elevated lipid peroxidation.
Yamamoto
K
K
Department of Internal Medicine, Saga Medical University School of Medicine, Japan.
Fukuda
N
N
Shiroi
S
S
Shiotsuki
Y
Y
Nagata
Y
Y
Tani
T
T
Sakai
T
T
D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D006937:Hypercholesterolemia / Q000139:chemically induced* / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011341:Probucol / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D008076:Cholesterol, HDL; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D002784:Cholesterol; D011078:Polychlorinated Biphenyls; D011341:Probucol