Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds.
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.
Farombi
E O
EO
Drug Metabolism and Toxicology Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria. ofarombi@skannet.com
Adepoju
B F
BF
Ola-Davies
O E
OE
Emerole
G O
GO
D000284:Administration, Oral; D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D018890:Chemoprevention; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005506:Food Contamination; D007263:Infusions, Parenteral; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D005419:Flavonoids; D016604:Aflatoxin B1; C045492:kolaviron