Role of cysteine conjugation in vinylidene chloride-induced nephrotoxicity and hepatotoxicity in fasted rats.
Pretreatment of fasted rats with aminooxyacetic acid (AOAA, 0.25 mmol kg-1, i.p.), methimazole (MTZ, 0.35 mmol kg-1, i.p.) and acivicin (AT-125, 56 mumol kg-1, i.p.) 30 min prior to a 4-h inhalation exposure to 180-200 ppm or 150-180 ppm vinylidene chloride (VDC) was used to study the role of cysteine beta-lyase, cysteine conjugate S-oxidase and gamma-glutamyltranspeptidase (gamma-GT) in VDC-induced liver and kidney toxicity. Pretreatment with AOAA reduced by 65-95% those increases in serum alanine aminotransferase (ALAT), glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) caused by exposure to 180-200 ppm VDC. This pretreatment also prevented VDC-induced increases in aspartate aminotransferase (ASAT) and N-acetyl-beta-d-glucosaminidase (NAG) activities and in the concentration of beta 2-microglobulin (beta 2-m) in 24-h urine samples. There was only a slight potentiation of VDC-induced liver and renal toxicities by MTZ given before exposure to 180-200 ppm VDC, but potentiation became significant (40-80%) when MTZ was administered before a slightly lower level of exposure (150-180 ppm). Pretreatment with AT-125 did not significantly change the liver and renal effects of exposure to 180-200 ppm VDC. These results suggest that the formation of a cysteine conjugate may be involved in the renal and liver toxicity of VDC in fasted rats.
Cavelier
L
L
Institut National de Recherche et de Sécurité, Vandeouvre, France.
Bonnet
P
P
Morel
G
G
de Ceaurriz
J
J
D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury; D003545:Cysteine / Q000378:metabolism*; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D005215:Fasting; D007674:Kidney Diseases / Q000139:chemically induced*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004000:Dichloroethylenes; C029297:vinylidene chloride; D003545:Cysteine