Pulmonary induction of proinflammatory mediators following the rat exposure to benzo(a)pyrene-coated onto Fe 2O 3 particles

Abstract

Epidemiological evidence firmly implicated an interactive effect between Fe 2O 3 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 Fe 2O 3 (3 mg), B(a)P (3 mg) or B(a)P (3 mg)-coated onto Fe 2O 3 (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-α; interleukin-1 beta, IL-1β; nitric oxide, NO) in lungs. In addition, mRNA expressions of TNF-α, IL-1β and inductible nitric oxide synthase (iNOS) were evaluated. Our results show that exposure to Fe 2O 3 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 Fe 2O 3, B(a)P or B(a)P-coated onto Fe 2O 3 particles significantly increased both mRNA expression and/or synthesis of inflammatory mediators. The main findings of this work were that the association of Fe 2O 3 and B(a)P induces more pronounced induction of inflammatory mediators (IL-1β secretion, P<0.01; IL-1β 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 Fe 2O 3 and B(a)P is more deleterious in lungs than exposure to B(a)P alone.