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.

Animals↗

PubMedDate not supplied

Hepatotoxicity of N, N-dimethylformamide in rats following intraperitoneal or inhalation routes of administration.

Male Sprague-Dawley rats were administered a single intraperitoneal injection of N, N-dimethylformamide (DMF, 0.01-1.5 g kg-1) or were exposed for 4 h to DMF vapours (75-900 ppm). The serum activities of the enzymes sorbitol deshydrogenase and glutamate deshydrogenase were used as indicators of liver damage, and were determined at 24, 48 or 72 h post-treatment. Following either route of administration DMF caused concentration-dependent elevations in enzyme activities, the maxima of which occurred later after administration of higher concentrations of DMF than after lower concentrations.

Administration, Inhalation↗

PubMedDate not supplied

Postnatal hepatic and renal consequences of in utero exposure to halothane or its oxidative metabolite trifluoroacetic acid in the rat.

In utero exposure of rats to low levels of the anaesthetic halothane has been reported to produce ultrastructural changes in the liver and kidney at birth. The current study examined the postnatal functional capacities of the liver and the kidney following prenatal exposure to halothane. Halothane or its oxidative metabolite trifluoroacetic acid (TFAA) were given to Sprague-Dawley rats on gestational days 10-20. Halothane was administered by inhalation at concentration of 50 or 500 ppm 6 h-1 day-1, and TFAA was administered by gavage at doses of 75 or 150 mg kg-1 day-1. The exposed offsprings were examined on postnatal days 3, 12 or 49 for hepatic and renal biochemistry and/or function through measurements of several serum and urinary parameters. Neither halothane nor TFAA treatments had statistically significant effect on litter size, neonatal survival or postnatal growth. Both prenatal halothane and TFAA exposure produced changes in liver biochemistry of newborns, as indicated by significant increases in the serum activities of glutamate dehydrogenase and aspartate aminotransferase. In addition, TFAA caused a functional deficit of the proximal tubule in newborns, as evidenced by the significant increase in the urinary excretion of beta 2-microglobulin. However, these hepatic and renal alterations were restricted to the early postnatal period and were no longer observed by postnatal day 49. It is concluded that prenatal exposure to relatively low levels of halothane can cause slight and transient changes in the neonatal rat liver.

Age Factors↗