EFFECT OF DIETARY PROTEIN AND SULFUR-CONTAINING AMINO ACIDS ON URINARY METABOLITES IN RATS INJECTED WITH CHLOROBENZENE

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Rats were fed for 10 days a 10 or 20% casein diet, or the diets with 0.3% DL-methionine or L-cystine. Rats fed the 20% casein exceeded those fed, the 10% casein in growth, hepatic glutathione (GSH) levels, and microsomal drug-metabolizing activities including cytochrome P-450, aminopyrine N-demethylase, and aniline hydroxylase. Supplement with methionine or cystine had significantly elevated hepatic GSH, regardless of the casein content. After the feeding, rats were intraperitoneally injected with chlorobenzene (0.5 mmol/kg body weight), and the urinary metabolites (4-chlorophenylmercapturic acid (4-CPMA), 2-, 3- and 4-chlorophenol (CPs), 4-chlorocatechol (4-CC), and 2-, 3- and 4-chlorophenylmethylsulfide (CPMSs)) were measured for 24 hours post-injection. Rats fed the 20% casein exceeded those fed the 10% casein in 4-CPMA, CPs, and in total urinary metabolites. Supplement with methionine or cystine to the 10% casein significantly increased 4-CPMA and decreased 4-CC. Supplement with methionine or cystine to the 20% casein also significantly increased 4-CPMA excretion, but had no effect on urinary 4-CC. The highest urinary excretion of CPMSs was observed in rats fed the 10% casein. Both increase of dietary protein and addition of the sulfur-containing amino acids decreased urinary CPMSs. These results indicate that total urinary metabolites are strongly associated with the microsomal drug-metabolizing activity, formation of the mercapturic acid is dependent on the hepatic GSH level, and the urinary CPMS level is independent on the mercapturic acid formation.