Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats.
1. In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate-induced damage to microsomal lipids was investigated. 2. Lipoprotein resistance to copper-induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron-treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron-treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron-treated rats with an attendant significant increase in the total anti-oxidant activity compared with control. 3. In vitro, kolaviron (10-60 micromol/L) inhibited the Cu2+-induced oxidation of rat serum lipoprotein in a concentration-dependent manner. Kolaviron, at 20 and 60 micromol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 micromol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 micromol/L) elicited a 53% increase in lag time, whereas 40 and 60 micromol/L kolaviron produced 38 and 88% decreases in slope, respectively. 4. Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration-dependent manner. Kolaviron at the highest dose tested (90 micromol/L) had a significant chelating effect on Fe2+ (78%). 5. In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti-oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis.
Farombi
E O
EO
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria. ofarombi@skannet.com
Nwaokeafor
I A
IA
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D002614:Chelating Agents; D005419:Flavonoids; D008074:Lipoproteins; D008563:Membrane Lipids; D003300:Copper; D007501:Iron; C045492:kolaviron