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Effects of buthionine sulfoximine on the development of ozone-induced pulmonary fibrosis

Journal Article · · Exp. Mol. Pathol.; (United States)
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The capacity of reduced glutathione (GSH) to protect lung tissue against ozone-induced pulmonary fibrosis was investigated. Male B6C3F1 mice were exposed to 0, 0.2, 0.5, and 1.0 ppm ozone for 23 hr/day for 14 days. During exposures and/or for a period of 90 days after exposures, subgroups of mice at each exposure level were given drinking water containing 30 mM L-buthionine-S,R-sulfoximine (BSO) to lower in vivo levels of GSH. These BSO treatments reduced blood glutamylcysteine synthetase (GCS) activity (regulatory enzyme for GSH biosynthesis) and lung nonprotein sulfhydryl (NPSH) levels in nonexposed animals by approximately half. In contrast, ozone exposures increased blood GCS activity and lung NPSH levels in a concentration-dependent manner, with smaller increases in the BSO-treated mice. Immediately after exposures, an ozone-related inflammatory response was seen in lungs, but no histopathological signs of developing fibrosis were evident. Ninety days later, mice exposed to 1 ppm ozone and not treated with BSO had modest evidence of pulmonary fibrosis. Mice exposed to 1 ppm ozone and treated with BSO during this post-exposure period (regardless of BSO treatment during exposures) showed histopathological evidence of exacerbated pulmonary fibrosis, compared to similarly exposed mice not treated with BSO postexposure. These results indicated that interference with the body's normal defense mechanisms against oxidant damage, including suppression of GSH biosynthesis, exacerbates the subsequent development of pulmonary fibrosis.
Research Organization:
Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)
OSTI ID:
6540050
Journal Information:
Exp. Mol. Pathol.; (United States), Journal Name: Exp. Mol. Pathol.; (United States) Vol. 49:2; ISSN EXMPA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIMETABOLITES
BIOLOGICAL EFFECTS
BODY
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
FIBROSIS
GLUTATHIONE
LUNGS
MAMMALS
METABOLISM
MICE
ORGANIC COMPOUNDS
ORGANS
OZONE
PATHOLOGICAL CHANGES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADICALS
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
RODENTS
SULFHYDRYL RADICALS
TOXICITY
VERTEBRATES