title: 1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, India.
authors.forename: Mahendrakumar Chandrasekharappa
authors.initials: MC
authors.lastname: Banakar
authors.forename: Suresh Kanna
authors.initials: SK
authors.lastname: Paramasivan
authors.forename: Mitali Basu
authors.initials: MB
authors.lastname: Chattopadhyay
authors.forename: Subrata
authors.initials: S
authors.lastname: Datta
authors.forename: Prabir
authors.initials: P
authors.lastname: Chakraborty
authors.forename: Malay
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Kalaiselvi
authors.initials: K
authors.lastname: Kannan
authors.forename: Elayaraja
authors.initials: E
authors.lastname: Thygarajan
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism*; D002273:Carcinogens; D020552:Comet Assay; D004249:DNA Damage; D004032:Diet; D004052:Diethylnitrosamine / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010634:Phenobarbital / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: C116441:2-methyl-1,25-dihydroxyvitamin D3; D000477:Alkylating Agents; D000927:Anticonvulsants; D000975:Antioxidants; D002273:Carcinogens; D014807:Vitamin D; D004052:Diethylnitrosamine; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D010634:Phenobarbital