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.
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032, India. ranjan_basak@hotmail.com
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R
Basak
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Bhattacharya
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M
Chatterjee
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