Abstract
Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation in the lungs of rats, and determined the effect of an antioxidant and of a glucocorticosteroid in Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar epithelium as compared with controls exposed to filtered air with a maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 +/- 1.3% (percent of nuclear cells expressing PCNA) to 4.4 +/- 1.3% (mean +/- SEM; p < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index in bronchial epithelium, from 19.2 +/- 2.3% to 10.9 +/- 2.6% (p < 0.05). Dexamethasone but not apocynin inhibited ozone-induced neutrophil influx. Rats exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expressed a lower PCNA index in bronchial epithelium than did rats exposed only once at 1.9 +/- 0.7% versus 6.0 +/- 0.9%, respectively (p < 0.05). The proliferative epithelial response following a single exposure to ozone is modulated through oxidative and inflammatory mechanisms probably involving neutrophils.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetophenones / administration & dosage
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Acetophenones / pharmacology*
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Administration, Oral
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Air Pollutants / adverse effects*
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Animals
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Anti-Inflammatory Agents / administration & dosage
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Antioxidants / administration & dosage
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Antioxidants / pharmacology*
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Bronchi / drug effects
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Bronchi / pathology
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Cell Division / drug effects
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Chemotaxis, Leukocyte / drug effects
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Dexamethasone / administration & dosage
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Dexamethasone / pharmacology*
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / pharmacology
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Epithelium / drug effects
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Epithelium / pathology
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Gene Expression Regulation
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Glucocorticoids / administration & dosage
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Glucocorticoids / pharmacology*
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Immunohistochemistry
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Inflammation
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Injections, Intraperitoneal
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Lung / drug effects*
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Lung / pathology
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Male
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NADP / antagonists & inhibitors
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Neutrophils / drug effects
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Oxidants, Photochemical / adverse effects*
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Oxidation-Reduction
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Ozone / adverse effects*
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Proliferating Cell Nuclear Antigen / analysis
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Proliferating Cell Nuclear Antigen / genetics
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Pulmonary Alveoli / drug effects
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Pulmonary Alveoli / pathology
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Rats
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Rats, Inbred BN
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Time Factors
Substances
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Acetophenones
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Air Pollutants
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Anti-Inflammatory Agents
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Anti-Inflammatory Agents, Non-Steroidal
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Antioxidants
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Enzyme Inhibitors
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Glucocorticoids
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Oxidants, Photochemical
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Proliferating Cell Nuclear Antigen
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NADP
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Ozone
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Dexamethasone
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acetovanillone