Combined supplementation of vanadium and 1alpha,25-dihydroxyvitamin D3 inhibit placental glutathione S-transferase positive foci in rat liver carcinogenesis.
The combined effects of vanadium (V) and 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 at the dose of 3 microg/ml in propylene glycol per os twice a week (Group E and F) or both V and 1,25(OH)2D3 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)2D3 (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)2D3 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)2D3 can able to minimize the appearance of nodules as well and maintain the normal cellular architecture than V and 1,25(OH)2D3 when given alone. These results suggest that, when given together V and 1,25(OH)2D3 could be the chemopreventive agents for rat liver carcinogenesis.
Basak
R
R
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
Chatterjee
M
M
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens; D004052:Diethylnitrosamine; D004347:Drug Interactions; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D008113:Liver Neoplasms; D008297:Male; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D010634:Phenobarbital; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014639:Vanadium / Q000627:therapeutic use*; D014881:Water Supply
D002273:Carcinogens; D014639:Vanadium; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D002117:Calcitriol; D010634:Phenobarbital