Mineral dust exposure and free radical-mediated lung damage.
Chronic exposure to several types of mineral dust particles induces an inflammatory reaction in the lung. Dust particles activate alveolar macrophages and prime leukocytes (neutrophils, eosinophils, and basophils), leading to an enhanced release of reactive oxygen species. Sometimes mineral dust particles also contain radicals. Reactive oxygen species (superoxide anion radical, hydrogen peroxide, hydroxyl radical, and singlet oxygen) may lead to tissue damage. These are able to break DNA strands, to destroy proteins, and to induce the process of lipid peroxidation. The effects of oxygen radicals on the beta-adrenergic and muscarinic receptor response of the guinea pig and rat tracheal strip are described. The beta-adrenergic receptor response appeared to be more susceptible to oxidative stress than the muscarinic receptor response. This may lead to an autonomic imbalance on exposure to oxygen radicals. The lipid peroxidation product 4-hydroxy-2,3-trans-nonenal diminished the beta-adrenergic responsiveness in guinea pig tracheal preparations. Histologic examinations indicated that at low concentrations of cumene hydroperoxide (10(-4) M) the epithelial layer of rat trachea was already destroyed, whereas no effect on the muscarinic response was found. Oxygen radical-mediated damage in lung tissue may lead to lung emphysema, hyperresponsiveness, and hypersensitivity. Pharmacotherapeutic interventions that prevent initiation or propagation of these free radical reactions may have a beneficial effect in mineral dust-associated lung disease.
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
C J
CJ
Doelman
R
R
Leurs
W C
WC
Oosterom
A
A
Bast
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004249:DNA Damage; D004391:Dust / Q000009:adverse effects*; D004781:Environmental Exposure; D005609:Free Radicals; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D015227:Lipid Peroxidation; D008903:Minerals; D010084:Oxidation-Reduction; D011014:Pneumonia / Q000378:metabolism*; D051381:Rats
D000975:Antioxidants; D004391:Dust; D005609:Free Radicals; D008903:Minerals