1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital.
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.
Banakar
Mahendrakumar Chandrasekharappa
MC
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, India.
Paramasivan
Suresh Kanna
SK
Chattopadhyay
Mitali Basu
MB
Datta
Subrata
S
Chakraborty
Prabir
P
Chatterjee
Malay
M
Kannan
Kalaiselvi
K
Thygarajan
Elayaraja
E
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*
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