Combined supplementation of vanadium and 1alpha,25-dihydroxyvitamin D(3) inhibit diethylnitrosamine-induced rat liver carcinogenesis

A combination of a differentiation-inducing agent like 1alpha, 25-dihydroxyvitamin D(3) 1,25(OH)(2)D(3)] with a compound that blocks entry of calcium into cells like vanadium (V) may offer a new approach to differentiation therapy and address the problem of hypercalcemia. Initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of diethylnitrosamine (DEN) (200 mg/kg b.wt.) in male Sprague-Dawley rats. Supplementation of V, 1, 25(OH)(2)D(3), or both V and 1,25(OH)(2)D(3) were started 4 weeks prior to DEN injection and continued thereafter till 20th week. It was observed that supplementation of V (0.5 ppm) in drinking water ad libitum or 1,25(OH)(2)D(3) (3 microg/ml propylene glycol) per os twice weekly for the entire period of the experiment significantly reduces the number and size of hyperplastic nodules while the combination treatment offered an additive effect in reducing it to 37.5% from 83.3%. V-1,25(OH)(2)D(3) combination was also effective in elevating the level of hepatic microsomal cytochrome P-450 (Cyt. P-450) (P<0.001). Moreover, A significant reduced level of cytosolic glutathione (GSH) (P<0.001) and glutathione S-transferase (GST) (P<0.001) activity as well as reduction in the appearance of gamma-glutamyltranspeptidase (GGT)-positive foci (P<0.001) as compared to carcinogen control were observed in V plus 1, 25(OH)(2)D(3) treated group. These results suggest that V may be useful in combination with 1,25(OH)(2)D(3) in the inhibition of experimental rat hepatocarcinogenesis.