Modulation of silica-induced lung injury by reducing lung non-protein sulfhydryls with buthionine sulfoximine.
A role for non-protein sulfhydryl moieties (NPSH) (e.g., glutathione) in silica (SI)-induced cellular inflammation and fibrosis was examined in C57Bl/6 mice depleted of lung NPSH by buthionine sulfoximine (BSO). Lung NPSH levels in the BSO-treated groups were reduced to approx. 50% of the non-BSO-treated animals. In BSO-treated SI-injected (2 mg/mouse) animals, the number of pulmonary alveolar macrophages (PAM) lavaged from the lungs was significantly increased on day 1 and decreased on day 7. Moreover, BSO-treated SI-exposed mice evidenced significantly more lavage protein and albumin on days 1 and 3, respectively, than non-BSO-treated SI-exposed mice. SI-induced collagen deposition, however, was decreased by 18% in the BSO-treated animals. These data suggest that lung NPSH lessens the potential of silica to elicit acute lung injury.
Section of Pharmacology/Toxicology, School of Pharmacy, University of Connecticut, Storrs 06269.
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Lombard-Gillooly
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Hubbard
D000818:Animals; D019328:Buthionine Sulfoximine; D003094:Collagen / Q000378:metabolism; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D012822:Silicon Dioxide / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D012822:Silicon Dioxide; D003094:Collagen