Literature DB >> 15112340

1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital.

Mahendrakumar Chandrasekharappa Banakar1, Suresh Kanna Paramasivan, Mitali Basu Chattopadhyay, Subrata Datta, Prabir Chakraborty, Malay Chatterjee, Kalaiselvi Kannan, Elayaraja Thygarajan.   

Abstract

AIM: To investigate the chemopreventive effects of 1alpha, 25-dihydroxyvitamin D(3) 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 1alpha, 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 microg/100 microL propylene glycol per one single dose (os) twice a week. Group E received the treatment of 1alpha, 25-(OH)2D3 at the same dose mentioned as above for 15 wk. The rats in group D and F received 1alpha, 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 1alpha, 25-dihydroxyvitaminD2 showed a significant (P<0.01) decrease in L:W ratio of DNA mass tailed cells. Furthermore, 1alpha, 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 1alpha, 25-dihydroxyvitaminD2.
CONCLUSION: Supplementations of 1alpha, 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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Year:  2004        PMID: 15112340      PMCID: PMC4622764          DOI: 10.3748/wjg.v10.i9.1268

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


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