Protective role of AKBA against benzo(a)pyrene-induced lung carcinogenesis by modulating biotransformation enzymes and oxidative stress.

ABSTRACT

The present study was designed to explore the chemopreventive potential of 3-acetyl-11-keto-ß-boswellic acid (AKBA) during the initiation and promotion stage of lung carcinogenesis induced by benzo(a)pyrene (BaP) in female Sprague Dawley rats. BaP was administered at a dose level of 50 mg/kg b.wt. twice a week orally in olive oil for 4 weeks. AKBA administration was started 4 weeks before BaP treatment and continued for another 8 weeks at a dose level of 50 mg/kg b.wt. orally in olive oil three times a week. BaP treatment showed significantly increased in the activities of Phase I biotransformation enzymes (Cytochrome P450 , b5 , and aryl hydrocarbon hydrolase) and inhibited the activity of Phase II enzyme (glutathione-S-transferase). Also, a significant elevation in oxidative stress biomarkers lipid peroxidation, reactive oxygen species, and protein carbonyl content concentration. Further, an appreciable decrease was observed in the activities of endogenous antioxidant enzymes superoxide dismutase, CAT, GPx, GR, and a decline in nonenzymatic GSH levels. As a result of BaP induced oxidative stress, alteration in erythrocytes morphology was observed. Fourier transform infrared spectroscopy spectrum of lung tissue showed structural changes due to BaP exposure. Moreover, levels of tumor biomarkers such as total sialic acid, carcinoembryonic antigen, and alkaline phosphatase were significantly elevated following BaP treatment which was substantiated by alterations noticed in the histoarchitecture of lung tissue. Interestingly, AKBA administration to BaP treated rats appreciably alleviated the changes inflicted by BaP on various biochemical indices and histoarchitecture of lungs. Therefore, the study clearly revealed that AKBA by containing oxidative stress shall prove to be quite effective in providing chemoprevention against BaP induced lung carcinogenesis.