Pretreatment of fasted rats with aminooxyacetic acid (AOAA, 0.25 mmol kg-', i.p.), methimazole (MTZ, 0.35 mmol kg-I, i.p.) and acivicin (AT-125, 56 pmol kg-', 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 plyase, cysteine conjugate S-oxidase and y-glutamyltranspeptidase (yGT) 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-P-,-glucosaminidase (NAG) activities and in the concentration of p,-microglobulin (&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.