Azadirachta indica modulates carcinogen biotransformation and reduced glutathione at peri-initiation phase of benzo(a)pyrene induced murine forestomach tumorigenesis.
The present study evaluated the effects of aqueous Azadirachta indica leaf extract (AAILE) on the activities of certain phase I (cytochrome P450, cytochrome b(5) and aryl hydrocarbon hydroxylase) as well as phase II (glutathione-S-transferase and UDP-glucuronosyl transferase) biotransformation enzymes; and reduced glutathione (GSH) (in forestomach and hepatic tissues) during/after intra-gastric instillations of B(a)P in murine forestomach tumorigenesis bioassay protocol. The activities of phase I biotransformation enzymes were found to increase, whereas a decrease in GSH content as well as glutathione-S-transferase was observed in mice receiving only B(a)P during as well as 2 weeks after B(a)P instillations. The activity of UDP-glucuronosyltransferase decreased during B(a)P instillations, whereas after the latter, the activity increased when compared with the control mice. However, in mice that received AAILE along with B(a)P instillations, a decrease in phase I enzymes was accompanied by an increase in phase II enzymes as well as GSH contents. Only AAILE treatment reduced the activities of phase I biotransformation enzymes and enhanced the GSH contents as well as the activities of phase II enzymes. Observations of the present study seem to be quite significant and (when taken together with our earlier findings) provides evidence for A. indica mediated modulation of the peri-initiation phase of the process of forestomach tumorigenesis.
Gangar
Subhash Chander
SC
Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh, India.
Koul
Ashwani
A
D000818:Animals; D031601:Azadirachta / Q000737:chemistry*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity*; D004798:Enzymes / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*
D002273:Carcinogens; D004798:Enzymes; D001564:Benzo(a)pyrene; D005978:Glutathione