1 alpha,25-Dihydroxyvitamin D(3) inhibits rat liver ultrastructural changes in diethylnitrosamine-initiated and phenobarbital promoted rat hepatocarcinogenesis.
The active metabolite of vitamin D, 1 alpha,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)] has been receiving increasing attention and has come to the forefront of cancer chemoprevention research as being a regulator of cellular growth, differentiation and death. In the present study, attempts have been made to investigate the in vivo chemopreventive effect of 1,25(OH)(2)D(3) in two-stage rat liver carcinogenesis. Hepatocarcinogenesis was initiated with a single intraperitoneal injection of diethylnitrosamine [DEN] (200 mg/kg b. wt.) at week 4. After a brief recovery period of 2 weeks, all the DEN-treated rats were given phenobarbital (0.05%) in the basal diet and continued thereafter till the completion of the experiment. The results of our experiment showed that the rats which received 1,25(OH)(2)D(3) for 14 weeks (0.3 microg/100 microL propylene glycol, per os, twice a week), starting the treatment 4 weeks prior to DEN injection, exhibited maximum protective effect in maintaining the normal cellular architecture of the hepatocytes than the group of rats which received this micronutrient for only 9 weeks. Moreover, continuous supplementation of 1,25(OH)(2)D(3) maintains the concentration of hepatic microsomal cytochrome P-450 like that of normal vehicle control. Thus, long-term supplementation of 1,25(OH)(2)D(3) significantly (P < 0.001) inhibits hepatic cytosolic lipid peroxidation, thereby protecting the cell membranes from free-radical mediated damage. These results suggest that 1,25(OH)(2)D(3) is useful in the inhibition of rat liver carcinogenesis.
Basak
R
R
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032, India. ranjan_basak@hotmail.com
Bhattacharya
R
R
Chatterjee
M
M
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008854:Microscopy, Electron; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; D002117:Calcitriol; D010634:Phenobarbital