Pulmonary induction of proinflammatory mediators following the rat exposure to benzo(a)pyrene-coated onto Fe2O3 particles.
Epidemiological evidence firmly implicated an interactive effect between Fe2O3 and benzo(a)pyrene (B(a)P) in causing lung cancer. However, despite intensive investigation, the mechanism involved is not precisely established. Since the accumulation of reactive oxygen intermediates (ROI)-mediated damage and/or immune-induced injury might be a possible cause of lung cancer, we studied the oxidative and the inflammatory effects of Fe2O3 (3 mg), B(a)P (3 mg) or B(a)P (3 mg)-coated onto Fe2O3 (3 mg) particles on this relevant organ target in Sprague-Dawley rats. We investigated lipid peroxidation (malondialdehyde; MDA) and secretion of some inflammatory mediators (tumor necrosis factor-alpha, TNF-alpha; interleukin-1 beta, IL-1beta; nitric oxide, NO) in lungs. In addition, mRNA expressions of TNF-alpha, IL-1beta and inducible nitric oxide synthase (iNOS) were evaluated. Our results show that exposure to Fe2O3 and B(a)P, alone or in association, induced 2-fold increases in MDA production suggesting thereby oxidative stress conditions (P<0.01). Exposure to Fe2O3, B(a)P or B(a)P-coated onto Fe2O3 particles significantly increased both mRNA expression and/or synthesis of inflammatory mediators. The main findings of this work were that the association of Fe2O3 and B(a)P induces more pronounced induction of inflammatory mediators (IL-1beta secretion, P<0.01; IL-1beta mRNA expression, P<0.01; iNOS mRNA expression, P<0.05) than B(a)P by itself. Hence, our results may explain why concurrent exposure to Fe2O3 and B(a)P is more deleterious in lungs than exposure to B(a)P alone.
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GIP-CERESTE, Laboratoire Universitaire de Médecine du Travail et des Risques Professionnels, Faculté de Médecine-Pôle Recherche, 01, place de Verdun, 59045 Cedex, Lille, France.
Gosset
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Garry
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Marez
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Hannothiaux
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Shirali
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D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003470:Culture Media / Q000032:analysis; D004347:Drug Interactions; D005290:Ferric Compounds; D007375:Interleukin-1 / Q000032:analysis / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D003470:Culture Media; D005290:Ferric Compounds; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C000499:ferric oxide; D009569:Nitric Oxide; D001564:Benzo(a)pyrene; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat