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Pulmonary hydroxyproline content and production following treatment of mice with O,S,S-trimethyl phosphorodithioate
1Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712-1074.
Abstract:
The systemic administration of O,S,S-trimethyl phosphorodithioate (OSS), a contaminant of various organophosphorus insecticides, induces delayed damage to rat and mouse lung tissue. The lesion, particularly in the rat, closely resembles that produced by butylated hydroxytoluene (BHT) in mice. Although the time course of cell damage and repair has been studied in both species, it is not clear whether excess collagen, indicative of fibrosis, is deposited. Changes in pulmonary hydroxyproline content and synthesis, indices of collagen metabolism, were analysed in mice treated with 45 mg/kg OSS. A significant increase in total lung hydroxyproline was evident 21 days after treatment compared to both pair-fed and ad libitum controls. This increase was not augmented by subsequent treatment with 35 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or exposure to 70% oxygen for 7 days. The rate at which lung tissue synthesized hydroxyproline was increased 7-14 days after treatment with OSS. These data demonstrate that treatment of mice with OSS results in changes indicative of pulmonary fibrosis. However, in contrast to some other lung-toxic chemicals, this lesion was not enhanced by subsequent treatment with BCNU or hyperoxia.
Insights
O,S,S-trimethyl phosphorodithioate (OSS), an insecticide contaminant, causes delayed lung damage and fibrosis in mice. This pulmonary fibrosis, indicated by increased hydroxyproline, was not worsened by BCNU or hyperoxia.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Biochemistry
Background:
- O,S,S-trimethyl phosphorodithioate (OSS) is a contaminant found in organophosphorus insecticides.
- OSS induces delayed lung tissue damage in rats and mice, similar to butylated hydroxytoluene (BHT).
- Previous studies focused on cell damage and repair, but collagen deposition (fibrosis) remained unclear.
Purpose of the Study:
- To investigate whether OSS treatment leads to pulmonary fibrosis in mice.
- To analyze changes in pulmonary hydroxyproline content and synthesis as indicators of collagen metabolism.
Main Methods:
- Mice were treated with 45 mg/kg OSS.
- Hydroxyproline content and synthesis rates in lung tissue were measured at various time points.
- Some mice received subsequent treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or exposure to 70% oxygen.
Main Results:
- A significant increase in total lung hydroxyproline was observed 21 days post-OSS treatment.
- Hydroxyproline synthesis rates in lung tissue increased 7-14 days after OSS treatment.
- Neither BCNU treatment nor hyperoxia augmented the OSS-induced increase in lung hydroxyproline.
Conclusions:
- Treatment with OSS induces changes indicative of pulmonary fibrosis in mice.
- Unlike some other lung toxicants, OSS-induced pulmonary fibrosis is not enhanced by BCNU or hyperoxia.