title: Benzo(a)pyrene induces oxidative stress, pro-inflammatory cytokines, expression of nuclear factor-kappa B and deregulation of wnt/beta-catenin signaling in colons of BALB/c mice.
abstract: The incidence of colonic toxicity has been epidemiologically linked to the consumption of foods contaminated with benzo(a)pyrene (B[a]P). The present study investigated the effects of B[a]P on biomarkers of oxidative stress, inflammation and wnt-signaling in colon of BALB/c mice following exposure to 62.5, 125 and 250 mg/kg of B[a]P for 7 days by oral gavage. Exposure to B[a]P significantly decreased the colonic antioxidant enzymes activities and glutathione level with concomitant significant increase in myeloperoxidase activity, nitric oxide and lipid peroxidation levels. Colon histopathology results showed treatment-related lesions characterized by atrophy, mucosal ulceration and gland erosion in the B[a]P-treated mice. Immunohistochemistry analysis showed that B[a]P treatment increased the protein expression of nuclear factor kappa B, pro-inflammatory cytokines namely tumor necrosis factor alpha and interleukin-1β, as well as cyclooxygenase-2 and inducible nitric oxide synthase in the mice colon. Altered canonical wnt-signaling was confirmed by strong diaminobenzidine staining for p38 mitogen activated protein kinase, β-catenin expression and absence of adenomatous polyposis coli following B[a]P administration. The present data highlight that exposure to B[a]P induces colon injury via induction of oxidative and nitrosative stress, inflammatory biomarkers and dsyregulation wnt/β-catenin signaling, thus confirming the role of B[a]P in the pathogenesis of colonic toxicity.
authors.affiliation: Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Babajide O
authors.initials: BO
authors.lastname: Ajayi
authors.affiliation: Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria. Electronic address: dedac2001@yahoo.co.uk.
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Adedara
authors.affiliation: Drug Metabolism & Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria. Electronic address: olatunde_farombi@yahoo.com.
authors.forename: Ebenezer O
authors.initials: EO
authors.lastname: Farombi
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051153:Wnt Proteins; D051176:beta Catenin; D001564:Benzo(a)pyrene
keywords: Benzo(a)pyrene; Colon toxicity; Inflammation; Oxidative stress; wnt signaling