Antiproliferative and antioxidant potential of hesperetin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice

Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Chemoprevention, employing the use of natural, dietary or synthetic agents has become an appealing strategy to combat the increasing cases of cancers worldwide. The present study was designed to investigate the mechanism-based chemopreventive nature of hesperetin (HSP) against B[a]P induced lung carcinogenesis in Swiss albino mice. We analyzed the chemopreventive potential of HSP by estimating the status of lipid peroxidation (LPO), enzymic (SOD, CAT, GPx, GR, and GST), nonenzymic antioxidants (GSH, Vit C and Vit E), proinflammatory cytokine (TNF-alpha), western blotting (CYP1A1, PCNA, Nrf2 and NF-kappa B expression) and histopathology of lung tissues of control and experimental mice. Administration of B[a]P (50 mg/kg, p.o.) resulted in an increase in lung weight, LPO with concomitant decrease in body weight, enzymic (SOD, CAT, GPx, GR, and GST) and non-enzymic (GSH, Vit C and Vit E) antioxidants. Histological examination of lungs revealed severe alveolar and bronchiolar damages in B[a]P-induced mice. Further, elevated levels of TNF-alpha along with activated expression of NF-kappa B, PCNA and CYP1A1, and downregulation of Nrf2 was observed in B[a]P intoxicated animals. Pre- and post-treatment with HSP effectively suppressed B[a]P induced lung carcinoma and the associated preneoplastic lesions by alleviating LPO, modulating antioxidants and decreasing the expression of NF-kappa B, PCNA and CYP1A1. These findings demonstrate that HSP possesses a potential chemopreventive activity against B[a]P induced lung cancer and this is attributed to its free radical scavenging, antioxidant, anti-inflammatory and antiproliferative properties. (C) 2015 Elsevier Ireland Ltd. All rights reserved.