Influence Of Industrial Poisons And Drugs On The Activity Of Microsomal Enzymes.
National Institute of Occupational Safety and Health, U.S. Department of Health, Education and Welfare, Cincinnati, Ohio, Polish-American Agreement No. 05-013-2, 1977 Jun:113 pages
The effect of industrial poisons and commonly used drugs on microsomal enzyme activity were studied in Wistar-rats. Rats were given aniline (62533) at 50 milligrams per kilogram (mg/kg) a day for 30 days or 150mg/kg for 3 or 6 days subcutaneously. The rate of microsomal metabolism and the cytochrome-P-450 content were determined after treatment. The roles of the microsomal enzyme inducers phenobarbital (50066) and 3,4-benzpyrene (50328) and the inhibitors SKF-525-A (62680) and cobaltous-chloride (7646799) were studied during aniline metabolism. Azobenzene (55801) was given intraperitoneally to rats at 150mg/kg a day for 3 or 4 days, 25mg/kg for 7 days, or 5mg/kg for 2 or 4 days. Microsomal metabolism of azobenzene and aniline was determined. The effects of common drugs chlordiazepoxide (58253) at 50 to 400mg/kg a day for 5 to 30 days and diazepam (439145) at 100 or 400mg/kg for 5 or 30 days were studied on liver microsomal enzyme activity. Ultrastructural studies were made of liver of rats given chlordiazepoxide. Effects of oxazepam (604751) at 200 or 400mg/kg for 5 or 30 days, phenacetin (62442) at 1 gram/kg for 6 or 14 days, or cyclobarbital (52313) at 150mg/kg for 4, 5, or 6 days were similarly studied. The effects of the drugs on metabolism of aniline and the development of tolerance were studied. Chronic exposure to aniline decreased cytochrome-P- 450 content in the liver and reduced the rate of microsomal metabolism of aniline in-vivo. Inducers stimulated aniline metabolism and inhibitors reduced it. Exposure to azobenzene also reduced microsomal metabolism of azobenzene and of aniline. The tranquilizers chlordiazepoxide and diazepam induced synthesis of microsomal enzymes in the liver. Treatment with chlordiazepoxide caused proliferation of smooth endoplasmic reticulum in parenchymal liver cells. Oxazepam, phenacetin, and cyclobarbital all stimulated microsomal metabolism in the liver. Disappearance of hypothermia and muscle relaxation rate of metabolism increased.
NIOSH-Author; Toxicology; Industrial-chemicals; Hepatic-microsomal-enzymes; Liver-microsomal-enzymes; Quantitative-analysis; Animal-studies; Metabolic-study; Reaction-rates; Quantitative-analysis;
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National Institute of Occupational Safety and Health, U.S. Department of Health, Education and Welfare, Cincinnati, Ohio, Polish-American Agreement No. 05-013-2, 113 pages, 97 references