Mechanisms for the hepatoprotective action of kolaviron: studies on hepatic enzymes, microsomal lipids and lipid peroxidation in carbontetrachloride-treated rats.
The present work examines the protective mechanisms of a biflavonoid fraction of an extract from Garcinia kola seeds, kolaviron, in rats treated with carbontetrachloride (CCl(4)). CCl(4)administered at a dose of 1.2 g kg(-1), three times a week for 2 weeks, significantly depressed the activities of microsomal aniline hydroxylase, aminopyrine N -demethylase, ethoxyresorufin O -demethylase and p -nitroanisole O -demethylase. Kolaviron (200 mg kg(-1)), administered for 14 days consecutively, inhibited (P<0.001) the CCl(4)mediated decrease in the activities of these enzymes by 60, 65, 55, and 63%, respectively. Kolaviron reduced the CCl(4)increase in the cholesterol/phospholipid ratio. Similarly, kolaviron attenuated the toxic onslaught imposed by CCl(4)on 5'nucleotidase, glucose 6-phosphatase (microsomal marker enzymes) and malondialdehyde formation by 41, 54 and 77%, respectively. Kolaviron elicited 168% and 234% increases in the activity of UDP-glucuronosyl transferase and glutathione S -transferase. Simultaneous administration of kolaviron with CCl(4)modulated the effect of CCl(4)on the activities of these enzymes. On the basis of the above data, it can be postulated that kolaviron exerts its protective action against carcinogen-induced liver damage, first, by acting as an in vivo natural antioxidant and, second, by enhancement of drug-detoxifying enzymes.
Farombi
E O
EO
Drug Metabolism and Toxicology Unit, Department of Biochemistry, University of Ibadan, Nigeria.
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002784:Cholesterol / Q000032:analysis; D005419:Flavonoids / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar
D005419:Flavonoids; D010743:Phospholipids; D010936:Plant Extracts; D002784:Cholesterol; D002251:Carbon Tetrachloride; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; C045492:kolaviron