Combined supplementation of vanadium and 1α,25-dihydroxyvitamin D3 inhibit placental glutathione S-transferase positive foci in rat liver carcinogenesis

The combined effects of vanadium (V) and 1 alpha ,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] in inhibiting diethylnitrosamine (DEN)-induced and phenobarbital (PB) promoted hepatocarcinogenesis were examined in male Sprague-Dawley rats. All the rats were subjected to 70% partial hepatectomy (PH) at week 4 and 24h later were administered either solvent trioctanoin (Group B, D, F and H) or 10 mg DEN/kg (Group A, C, E and G) by gavage. Briefly after two weeks of DEN administration, PB were administered (0.05% in basal diet) to all the DEN-treated rats and continued till the completion of the experiment. Supplementary V at the dose of 0.5 ppm in drinking water ad libitum (Group C and D), 1,25(OH)(2)D-3 at the dose of 3 mug/ml in propylene glycol per os twice a week (Group E and F) or both V and 1,25(OH)(2)D-3 at the same above given doses (Group G and H) were started 4 weeks prior to DEN administration (week 0) and continued thereafter till week 15. The expression of the number and area of altered hepatocyte foci (AHF) positive for placental glutathione S-transferase (GST-P) was maximum in DEN-treated and PB promoted group (Group A). V (Group C) and 1,25(OH)(2)D-3 (Group E) treatment significantly reduced the expression of GST-P-positive hepatocytes by 36.02% and 45.16% respectively but an additive protective action (61.46%) was found in Group G which received both V and 1,25(OH)(2)D-3 for the entire period of the study. Moreover, histopathological examination and the incidence of hepatic hyperplastic nodules showed that combined action of V and 1,25(OH)(2)D-3 can able to minimize the appearance of nodules as well and maintain the normal cellular architecture than V and 1,25(OH)(2)D-3 when given alone. These results suggest that, when given together V and 1,25(OH)(2)D-3 could be the chemopreventive agents for rat liver carcinogenesis. (C) 2000 Elsevier Science Inc. All rights reserved.