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Effects of hard metal on the nitric oxide pathway of rat lung.
Am J Respir Crit Care Med 1998 Mar; 157(3)(Suppl):A696
Occupational inhalation of hard metal (HM) induces several disorders including asthma and pulmonary fibrosis. Nitric oxide (NO) is a multi-functional messenger in the lung while the role of NO in HM induced pulmonary pathophysiology is unknown. We investigated the effect of an industrial HM mixture on the NO pathway in rat lungs. HM was instilled (Lt.) at 2.5 and 5 mg/100 g weight of rat while controls received saline. In another set, one group of rats were injected (i.p.) with LPS (0.lmg/100 g) while others received both LPS and HM. After 8 hr, the lungs were removed and homogenized. NO synthase (NOS) activity in the soluble and particulate fractions was determined by measuring the conversion of L-[14C] arginine to L-[14C] citrulline. HM caused a significant increase of NOS activity in the soluble fraction of LPS treated rats but not in rats not treated with LPS (non-LPS rats). At the same time, HM significantly decreased the particulate NOS activity of non-LPS rats while causing an increase in LPS induced particulate NOS activity. In Western blots, the control and HM lung homogenates showed no inducible NOS (iNOS) protein. But, after LPS treatment, iNOS protein appeared and its level was significantly increased by HM at the 2.5 mg dose. However, endothelial NOS protein level was not significantly altered by HM, LPS or HMILPS treatments. These findings suggest that HM induced alterations in the NO pathway may be involved in the pathophysiology of hard metal diseases.
Laboratory-animals; Animals; Animal-studies; Hard-metals; Oxides; Bronchial-asthma; Pulmonary-system-disorders; Fibrosis; Lung-disorders; Diseases; Respiratory-system-disorders
Conference/Symposia Proceedings; Abstract
Issue of Publication
American Journal of Respiratory and Critical Care Medicine
Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division