title: Antiproliferative and antioxidant potential of hesperetin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice.
abstract: 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-α), western blotting (CYP1A1, PCNA, Nrf2 and NF-κB 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-α along with activated expression of NF-κB, 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-κB, 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.
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India. Electronic address: laxmi.naren21@gmail.com.
authors.forename: Lakshmi Narendra
authors.initials: LN
authors.lastname: Bodduluru
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India.
authors.forename: Eshvendar Reddy
authors.initials: ER
authors.lastname: Kasala
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati 781032, Assam, India.
authors.forename: Chandana C
authors.initials: CC
authors.lastname: Barua
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India.
authors.forename: Kalyani Chowdary
authors.initials: KC
authors.lastname: Karnam
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India.
authors.forename: Vicky
authors.initials: V
authors.lastname: Dahiya
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India.
authors.forename: Maheswara
authors.initials: M
authors.lastname: Ellutla
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha; D001564:Benzo(a)pyrene; D006569:Hesperidin; D019363:Cytochrome P-450 CYP1A1; C013015:hesperetin
keywords: Benzo[a]pyrene; Chemoprevention; Flavonoids; Hesperetin; Lung cancer