Premium
Role of Cysteine Conjugation in Vinylidene Chloride‐induced Nephrotoxicity and Hepatotoxicity in Fasted Rats
Author(s) -
Cavelier L.,
Bonnet P.,
Morel G.,
Ceaurriz J. de
Publication year - 1996
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/(sici)1099-1263(199603)16:2<109::aid-jat308>3.0.co;2-9
Subject(s) - nephrotoxicity , cysteine , chemistry , toxicity , chloride , pharmacology , endocrinology , biochemistry , medicine , enzyme , organic chemistry
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 μmol 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 β‐lyase, cysteine conjugate S‐oxidase and γ‐glutamyltranspeptidase (γ‐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‐β‐d‐glucosaminidase (NAG) activities and in the concentration of β2‐microglobulin (β2‐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.