Effect of dietary protein and sulfur-containing amino acids on urinary metabolites in rats injected with chlorobenzene.
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.
Goto
H
H
Department of Public Health, Kansai Medical University, Osaka, Japan.
Yoshida
M
M
Nakazono
N
N
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002364:Caseins / Q000494:pharmacology; D002722:Chlorobenzenes / Q000493:pharmacokinetics / Q000652:urine*; D003553:Cystine / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004032:Diet; D004044:Dietary Proteins / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000603:Amino Acids, Sulfur; D002364:Caseins; D002722:Chlorobenzenes; D004044:Dietary Proteins; D003553:Cystine; D003577:Cytochrome P-450 Enzyme System; D008715:Methionine; D005978:Glutathione; C031294:chlorobenzene