Inhibition of 3'-methyl-4-dimethylaminoazobenzene-induced hepatocarcinogenesis in rat by dietary beta-carotene: changes in hepatic anti-oxidant defense enzyme levels.
The dietary administration of beta-carotene (BC) daily has been found to be highly effective in reducing hepatocarcinogenesis in male Sprague-Dawley rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-Met-DAB). The anti-cancer efficacy of BC was evaluated by estimating some possible pre-neoplastic and neoplastic hepatic anti-oxidant markers such as glutathione (GSH) and related enzymes, namely glutathione S-transferases (GSHT, with varying substrate specificities), gamma-glutamyl transpeptidase (GGT), glutathione peroxidase (GPX) and reductase. BC proved to be an effective anti-neoplastic substance in long-term treatment. Furthermore, BC limited the exponential increase of GSH, GGT, GSH-T and GPX both in the hyperplastic nodules (HNs) and surrounding liver (NNSP) areas compared with carcinogen control (3'-Met-DAB) rats during long-term treatment. Early marginal changes in GSH, GGT and GSHT (with 1-chloro-2,4-dinitrobenzene as a substrate) activities in BC-treated groups for 10 days compared with carcinogen (3'-Met-DAB once) control rats entail the participation of BC in the initial stages of hepatocarcinogenesis. A decrease in the number of hyperplastic nodules and the total liver parenchyma they occupy was observed in BC-treated groups. HNs and NNSP liver areas are directly correlated with hepatic BC and vitamin A content and with rates and patterns of hepatic anti-oxidant defense enzymes. Our results confirm that BC is protective in limiting the action of 3'-Met-DAB during the initiation phase of hepatocarcinogenesis.
Sarkar
A
A
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
Mukherjee
B
B
Chatterjee
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004032:Diet; D005979:Glutathione Peroxidase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008749:Methyldimethylaminoazobenzene; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014801:Vitamin A / Q000378:metabolism / Q000494:pharmacology; D019207:beta Carotene; D005723:gamma-Glutamyltransferase / Q000032:analysis
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D008749:Methyldimethylaminoazobenzene; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase