Preventive effects of Azadirachta indica on benzo(a)pyrene-DNA adduct formation in murine forestomach and hepatic tissues.
In the present investigation, the effects of aqueous Azadirachta indica leaf extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation, the status of biotransformation enzymes and reduced glutathione (GSH) content were evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the liver of AAILE treated mice compared with their control counterparts. After AAILE treatment, the cytochrome P450 content decreased, whereas the GSH content increased significantly in the hepatic tissue. In the forestomach as well as in the liver, the cytochrome b5 content declined, whereas an increase in glutathione-S-transferase (GST) activity was observed in both tissues. These observations suggested that AAILE may have reduced the metabolic activation of (3)H-B(a)P with enhanced detoxification of its active metabolites, hence the observed decrease in the levels of (3)H-B(a)P-DNA adducts. These molecular and biochemical modulations observed at the initiation phase of carcinogenesis seems to be significant and could be correlated with the chemopreventive effects of A. indica against B(a)P induced forestomach tumorigenesis.
Gangar
Subhash Chander
SC
Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh 160014, India.
Sandhir
Rajat
R
Rai
Durg Vijay
DV
Koul
Ashwani
A
D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031601:Azadirachta / Q000737:chemistry*; D001564:Benzo(a)pyrene / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D013270:Stomach / Q000187:drug effects*
D016587:Antimutagenic Agents; D018736:DNA Adducts; D010936:Plant Extracts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D005982:Glutathione Transferase; D005978:Glutathione