Comparative Biochemistry and Metabolism. Part 2. Naphthalene Lung Toxicity
Abstract
Earlier studies have shown that cytochrome P-450 dependent metabolism of the volatile aromatic hydrocarbon, naphthalene, results in dose dependent bronchiolar necrosis in mice and in the formation of reactive metabolites which deplete cellular glutathione and become bound covalently to tissue macromolecules. Pretreatments which altered the severity of bronchiolar necrosis altered the extent of covalent binding in the lung. However, the overall levels of covalently bound metabolites in liver and kidney (non target tissues) were higher than in lung suggesting that several different reactive metabolites might be formed in the tissue but not all are toxicologically important or that the liver may contribute substantially to the overall levels of covalent binding in extrahepatic organs. To examine potential differences in target vs. non target organ metabolism of naphthalene to chemically reactive metabolites in vitro a high pressure liquid chromatographic method has been developed to separate and quantitate glutathione adducts formed from reactive naphthalene metabolites generated in microsomal or tissue slice incubations. At least three such metabolites were found in microsomes or tissue slices; these have not yet been identified.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1982
- Accession Number
- ADA120007
Entities
People
- Alan R. Buckpitt
Organizations
- University of California, Irvine