Comparative Biochemistry and Metabolism. Part 2. Naphthalene Lung Toxicity
Abstract
Earlier studies have shown that intraperitoneal administration of naphthalene causes selective pulmonary bronchiolar necrosis in mice and have suggested a role for reactive naphthalene metabolites in the tissue damage. These studies have been extended to show that covalent binding of reactive naphthalene metabolites to tissue macromolecules in lung, liver and kidney is dose-dependent. High levels of covalent binding occur only after tissue glutathione levels are depleted substantially and only at doses of 200 mg/kg and above. The 200 mg/kg dose is the lowest dose at which lung lesions are observed. Piperonyl butoxide pretreatment decreases pulmonary damage and covalent binding and partially blocks glutathione depletion by 400 mg/kg naphthalene. In comparison, SKF 525 A pretreatment decreased covalent binding levels to a much smaller extent and failed to alter glutathione depletion or pulmonary damage after 400 mg/kg naphthalene. When compared to vehicle pretreated controls, phenobarbital or 3-methylcholanthrene pretreatment produced no change in the severity of lung damage after doses of naphthalene ranging from 50 to 400 mg/kg nor did these inducers alter covalent binding at doses of naphthalene of 200 mg/ kg or less. Pretreatment of mice with p-xylene preferentially inactivated pulmonary cytochrome p450 and blocked naphthalene induced lung damage but failed to selectively decrease covalent binding of reactive metabolites in the lung. Current studies are continuing to examine the role of cytochrome P450 dependent metabolic activation of naphthalene in the lung in the bronchiolar damage.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1981
- Accession Number
- ADA107673
Entities
People
- Alan R. Buckpitt
Organizations
- University of California, Irvine