Effect of buthionine sulfoximine on orthophenylphenol-induced hepato- and nephrotoxic potential in male rats.
A single oral administration of orthophenyl-phenol (OPP, 1400 mg/kg; about half the LD50) to male Fischer 344 rats produced an elevation of serum transaminase activity 24 h later. Pretreatment with L-buthionine-S,R-sulfoximine (BSO, 900 mg/kg) in the OPP-treated rats potentiated the hepatic and renal damage which was accompanied by necrosis. Six hours after the administration of OPP (700 or 1400 mg/kg), hepatic and renal glutathione (GSH) levels decreased with increasing dosage. Hepatic GSH depletion with OPP was enhanced with BSO pretreatment and the recovery of GSH in both organs was slow in the high-dose OPP group. These results suggest that hepatic and renal damage is associated with a serious and prolonged GSH depletion. When either phenyl-p-benzoquinone (PBQ) or phenylhydroquinone (PHQ), which are intermediates of OPP, was administered orally to rats at 700 or 1400 mg/kg, the mortality with the high dose of PBQ was 75% at 24 h. The serum transaminase activity and UN level increased with the low dose of PBQ, accompanied by necrotic hepatocytes. The toxic effects of PHQ on kidney or liver were less than those on PBQ. These observations suggest that the liver and kidney may be target organs for toxic actions of a large dose of OPP and its intermediate, PBQ.
Nakagawa
Y
Y
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Tayama
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001713:Biphenyl Compounds / Q000633:toxicity*; D019328:Buthionine Sulfoximine; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D001713:Biphenyl Compounds; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C004369:2-phenylphenol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione