Vitamin D3 suppresses the early stages of chemically induced hepatocarcinogenesis in rats: a dose-response analysis

Abstract

Background: The aim of this study was to investigate dose-response effects of vitamin D3 (VD3) supplementation on the early stages of diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced hepatocarcinogenesis in rats. Methods: The animals were randomly allocated into six experimental groups (10 rats each) treated as follows: group 1: no treatment; groups 2–6: single intraperitoneal injection of N-diethylnitrosamine; groups 2–6: intragastric CCl4; groups 3–6: intragastric VD3 at 10,000, 20,000, 40,000, and 60,000 IU/kg b.w., respectively. Results: Serum 25-hydroxyvitamin D (25-OHD) levels in the VD3-supplemented groups were significantly higher than those in the control groups (G1 and G2, p < 0.001). Serum levels of phosphate were higher in the groups supplemented with VD3 at 10,000 and 60,000 IU/kg (G3 and G6, p < 0.005). VD3 higher doses reduced cell proliferation and the number of larger placental glutathione S-transferase (GST-P)-positive hepatocellular preneoplastic lesions. Neither the DEN/CCl4 regimen nor the VD3 supplementation altered vitamin D receptor (VDR) protein expression in the liver. Conclusion: The results indicate that high-dose VD3 supplementation reduced the development of DEN/CCl4-induced preneoplastic lesions in the liver.