Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 1, 2004; 10(9): 1268-1275
Published online May 1, 2004. doi: 10.3748/wjg.v10.i9.1268
1α, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital
Mahendrakumar Chandrasekharappa Banakar, Suresh Kanna Paramasivan, Mitali Basu Chattopadhyay, Subrata Datta, Prabir Chakraborty, Malay Chatterjee, Kalaiselvi Kannan, Elayaraja Thygarajan
Mahendrakumar Chandrasekharappa Banakar, Suresh Kanna Paramasivan, Mitali Basu Chattopadhyay, Subrata Datta, Prabir Chakraborty, Malay Chatterjee, Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
Kalaiselvi Kannan, Elayaraja Thygarajan, Department of Environmental Science, PSG College of Arts and Science, Coimbatore 641014, Tamilnadu, India
Author contributions: All authors contributed equally to the work.
Supported by All India Council for Technical Education (AICTE), Govt of India and Veerasaiva Vidya Vardhaka Sangha (VVS), Bellary Karnataka, India
Correspondence to: Malay Chatterjee, PO 17028, Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, India. mcbiochem@yahoo.com
Telephone: +91-33-24146393 Fax: +91-33-24146393
Received: October 31, 2003
Revised: December 1, 2003
Accepted: December 30, 2003
Published online: May 1, 2004
Abstract

AIM: To investigate the chemopreventive effects of 1α, 25-dihydroxyvitamin D3 in diethylnitrosamine induced, phenobarbital promoted rat hepatocarcinogenesis.

METHODS: The rats were randomly divided into 6 different groups (A-F). Groups A, C and E rats received a single intraperitoneal (i.p) injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body mass in 9 g/L NaCl solution at 4 wk of age, while group B served as normal vehicle control received normal saline once. After a brief recovery of 2 wk, all the DEN treated rats were given phenobarbital (PB) at 0.5 g/L daily in the basal diet till wk 20. Group A was DEN control. Treatment of 1α, 25-(OH)2D3 in group C was started 4 wk prior to DEN injection and continued thereafter till wk 20 at a dose of 0.3 μg/100 μL propylene glycol per one single dose (os) twice a week. Group E received the treatment of 1α, 25-(OH)2D3 at the same dose mentioned as above for 15 wk. The rats in group D and F received 1α, 25-(OH)2D3 alone as in group C without DEN injection.

RESULTS: The comet assay showed statistically higher mean values for length to width ratios (L: W) of DNA mass and tailed cells (P < 0.01; P < 0.01 respectively) in DEN treated rats as compared to their normal controls. Continuous supplementation of 1α, 25-dihydroxyvitaminD3 showed a significant (P < 0.01) decrease in L:W ratio of DNA mass tailed cells. Furthermore, 1α, 25-(OH)2D3 supplementations elevated the super oxide dismutase (SOD) activity, hepatic malondialdehyde (MDA) level, reduced glutathione (GSH) and glutathione S-transferase (GST) activity (P < 0.01, P < 0.05, P < 0.05 and P < 0.05 respectively). As an endpoint marker histological changes were observed to establish the chemopreventive effects of 1α, 25-dihydroxyvitaminD3.

CONCLUSION: Supplementations of 1α, 25-(OH)2D3 has a marked protection against hepatic nodulogenesis, antioxidant enzymes and DNA damages in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.

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