1α,25-dihydroxyvitamin D_(3) prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital

AIM:To investigate the chemopreventive iffects of 1α,25-dihydroxyvitamin D3 in diethylnitrosamine induced,phenobarbital promoted rat hepatocarcinogenesis.METHODS:The rats were randomly divided into 6 different groups(A-F).Group A,C and E rats received a single intraperitoneal (i.p) injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body mass in 9 g/L NaCl solution at 4 wk of age ,while group B served as normal vehicle control received normal saline once.After a brief recovery of 2 WK, all the DEN treated rats were given phenobarbital (PB) at 0.5g/L daily in the basal diet till WK 20.Group C was started 4 wk prior to DEN injection and continued thereafter till wk 20 at a dose (os) twice a week.Group E received the treatment of 1α,25-(OH)2D3 at the same dose mentioned as above for 15 wk.The rats in group D and F received 1α,25-(OH)2D3 alone as in group C without DEN injection.RESULTS:The comet assay showed statistically higher mean values for length to width ratios (L:W) of DNA mass and tailed cells (p<0.01;p<0.01 respectively) in DEN treated rats as compared to their normal controls.Continuous supplementation of 1α,25-dihydroxyvitaminD3 showed a significant (p<0.01) decrease in L:W ratio of DNA mass tailed cells.Furthermore,1α,25-(OH)2D3 supplementations elevated the super oxide dismutase (SOD) activety,hepatic malondialdehyde(MDA) levle,reduced glutathione (GSH) and glutathione S-transferase (GST) activety (p<0.01,p<0.01,p<0.05 and p<0.05 respectively).As an endpoint marker histological changes were observed to establish the chemopreventive effects of 1α,25-dihydroxyvitaminD3.CONCLUSION:Supplementations of 1α,25-(OH)2D3 has a marked protection against hepatic nodelogenesis,antioxidant enzymes and DNA damages in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.