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The chemopreventive effects of kolaviron, a natural antioxidant bioflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats. Kolaviron administered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase (gamma-GT) by 62%, 56% and 72% respectively. Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1-treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and gamma-GT as well as lipid peroxidation caused by AFB1 (P<0.01). Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively. In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P<0.01). Pretreatment of rats with kolaviron, vitamins C and E alone did not exert genotoxicity assessed by the formation of micronucleated polychromatic erythrocytes (MNPCEs) (P>0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P<0.001) after 72 h. While vitamin C was effective in reducing AFB1-induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemopreventive agent against AFB1-induced genotoxicity and hepatic oxidative stress. Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.

The antioxidant and scavenging properties of kolaviron, a flavonoid extract of Garcinia kola seeds, were evaluated in a series of in vitro assays involving free radicals and reactive oxygen species. Kolaviron exhibited markedly reducing power and antioxidant activity by inhibiting the peroxidation of linoleic acid. Kolaviron exhibited 57% scavenging effect on superoxide at a concentration of 1 mg/ml and 85% scavenging effect on hydrogen peroxide at a concentration of 1.5 mg/ml. Similarly, kolaviron, at a concentration of 2 mg/ml, elicited an 89% scavenging effect on a,a-diphenylb-picrylhydrazyl radical, indicating that the extract has effective activities as a hydrogen donor and as a primary antioxidant to react with lipid radicals. Kolaviron reacted with hydroxyl radical ( . OH) by inhibiting deoxyribose oxidation induced by a Fenton-type reaction system (Fe 3+ + EDTA/H 2 O 2 /ascorbic acid). The second-order rate constant for the reaction with . OH was approximately 1.1 ¥ 10 10 M -1 sec -1 . Kolaviron was effective at preventing microsomal lipid peroxidation induced by iron/ascorbate in a concentration dependent manner. The overall antioxidant activity of kolaviron on lipid peroxidation might be attributed to its properties of scavenging free radicals and active oxygen species and may relate directly to prevention of propagation of in vivo lipid peroxidation.

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Kolaviron biflavonoids have demonstrated antihepatotoxic activity in animal studies. The present study investigated the possible chemopreventive potential of kolaviron in inhibiting aflatoxin B1 (AFB1) genotoxicity in HepG2 cells. Kolaviron inhibition of AFB1-induced cytotoxicity by clonogenic assay and genotoxicity by [3H]thymidine incorporation in unscheduled DNA synthesis were evaluated, including antioxidant potential of kolaviron determined by its reduction in the intracellular reactive oxygen species level induced by hydrogen peroxide. Induction of AFB1-detoxicating enzymes such as cytochrome P450 3A4 (3A4) and glutathione S-transferases (GSTs) A1-1/ A2-2 (alpha) and M1B (mu) was determined by reverse transcription polymerase chain reaction (RT-PCR) and northern blotting for the messages and western immunoblot analysis for protein. Kolaviron significantly (P < 0.01) and dose-dependently inhibited the cytotoxicity (by 71.6%) and genotoxicity (47.1%) of AFB1 in HepG2 cells. The antioxidant potential of kolaviron compared favourably with values for the standard antioxidant trolox C (53.8% at only 4.5 x 10(-2)-fold kolaviron concentration) but was below that of butylated hydroxyanisole (58.1% at a ninefold kolaviron concentration). It induced about threefold increases in the messages for 3A4 and GSTs alpha and mu, including a twofold increase in GSTalpha protein. Kolaviron may have chemopreventive potential in inhibition of human AFB1 genotoxicity and possibly hepatocarcinogenesis.