Azadirachta indica leaf extract modulates initiation phase of murine forestomach tumorigenesis

• Published in: Indian journal of biochemistry & biophysics 2007-08, Vol.44 (4), p.209
• Main Authors: Gangar, Subhash Chander, Koul, Ashwani
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Animals; Anticarcinogenic Agents - pharmacology; Aryl Hydrocarbon Hydroxylases - metabolism; Aspartate Aminotransferases - blood; Azadirachta - chemistry; Benzo(a)pyrene - toxicity; Carcinogens; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - drug effects; Ganglioside Galactosyltransferase - metabolism; L-Lactate Dehydrogenase - blood; Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; Liver - enzymology; Mice; Plant Extracts - pharmacology; Plant Leaves - chemistry; Stomach - enzymology; Stomach Neoplasms - chemically induced; Stomach Neoplasms - drug therapy
• ISSN: 0301-1208

The effects of aqueous Azadirachta indica leaf extract (AAILE) on benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis, B(a)P-DNA adduct formation and certain parameters of carcinogen biotransformation system in mice have been reported earlier from our laboratory. In this study, the effects of AAILE on the enzymes of B(a)P biotransformation, which play crucial role in initiation of chemical carcinogenesis - aryl hydrocarbon hydroxylase (AHH) and uridinediphosphoglucuronosyltransferase (UDP-glucuronosyltransferase) have been evaluated in murine forestomach and liver. In addition, lipid peroxidation (LPO) levels in forestomach as well as liver and the activities of tissue injury marker enzymes - lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase in the serum have also been evaluated. Oral administration of AAILE (100 mg/kg body wt for 2 weeks) reduces the AHH activity and enhances the UDP-glucuronosyltransferase activity in both the tissues, suggesting its potential in decreasing the activation and increasing the detoxification of carcinogens. The LPO levels decrease upon AAILE treatment in the hepatic tissue, suggesting its antioxidative and hence anti-carcinogenic effects. Non-significant alterations have been observed in tissue injury marker enzymes upon AAILE treatment, suggesting its safety at the given dose. In conclusion, AAILE appears to modulate initiation phase of carcinogenesis and may be suggested as safe and an effective agent for chemoprevention.