title: Anti-clastogenic activity of Azadirachta indica against benzo(a)pyrene in murine forestomach tumorigenesis bioassay.
abstract: Abstract: Present study evaluated the anti-clastogenic efficacy of Azadirchta indica (A. indica) against benzo(a)pyrene [B(a)P] in murine forestomach tumorigenesis bioassay protocol. Female Balb/c mice were divided into four groups (n = 8). Each mouse from B(a)P and B(a)P + A. indica groups received intragastric instillations of B(a)P at a dose of 40 mg/kg b. w. in 0.2 mL olive oil twice a week, starting from 3rd week to the end of 6th week of the experiment. Mice of control and A. indica groups received 0.2 mL olive oil in the same schedule as for B(a)P and B(a)P + A indica groups. Mice of A. indica and B(a)P + A. indica groups received oral doses of 100 mg/kg b. w. aqueous A. indica leaf extract (AAILE) on alternate days throughout the experiment. Two weeks after the last B(a)P instillation, mice were sacrificed and spleens were processed for micronucleus (MN) assay, while liver tissues were analyzed for lipid peroxidation (LPO), as well as antioxidant defense enzymes, namely: catalase, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx). The incidence of MN formation increased in spleen cells of mice that received only B(a)P instillations. In hepatic tissues, the extent of oxidative stress increased upon B(a)P instillations as was evidenced from enhanced LPO levels with concomitant decrease in antioxidant defense enzyme activities in mice that received only B(a)P instillations. Interestingly, A. indica treatment significantly reversed these effects as observed in mice receiving AAILE along with B(a)P when compared to only B(a)P receiving mice. Moreover, in only AAILE receiving mice, enhanced antioxidant defense with slightly decreased levels of LPO as well as MN incidences were observed. Observations of the present study suggest that A. indica exert anticlastogenic effects against B(a)P by modulating oxidative stress and antioxidant defense.
authors.affiliation: Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh, 160014, India.
authors.forename: Subhash Chander
authors.initials: SC
authors.lastname: Gangar
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.forename: Ashwani
authors.initials: A
authors.lastname: Koul
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D031601:Azadirachta / Q000737:chemistry*; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000517:prevention & control*
chemical_list: D016587:Antimutagenic Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D002273:Carcinogens; D010936:Plant Extracts; D001564:Benzo(a)pyrene