Metabolic normalization of alpha-ketoglutarate against N-nitrosodiethylamine-induced hepatocarcinogenesis in rats.
Chemoprevention of cancer is one of the reliable approaches to control the incidence of cancer. In the present study, we investigated the chemopreventive role of alpha-ketoglutarate (alpha-KG) during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. The activities of serum aspartate and alanine transaminases were found to be significantly higher in NDEA + CCl(4)-treated animals when compared with control animals. Administration of alpha-KG restored the activities of transaminases to near normal range. The levels of lipid peroxides, thiobarbituric acid reactive substances were decreased in the liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG reversed the lipid peroxide levels to near normal range. Levels of antioxidants, reduced glutathione and activities of its dependent enzymes, glutathione peroxidase and glutathione-S-transferase were found to be significantly higher in liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG administration positively modulated the antioxidant levels to near normal range. In conclusion, it can be suggested that alpha-KG exerts chemopreventive role which may attributable to its ability to positively modulate the transaminase activities and oxidant-antioxidant imbalance during hepatocarcinogenesis.
Dakshayani
K B
KB
Department of Biochemistry, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
Subramanian
P
P
Manivasagam
T
T
Mohamed Essa
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D004052:Diethylnitrosamine; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016588:Anticarcinogenic Agents; D007656:Ketoglutaric Acids; D017392:Thiobarbituric Acid Reactive Substances; D004052:Diethylnitrosamine; D002251:Carbon Tetrachloride; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione