Dichlorovinyl cysteine (DCVC)-induced enzymuria in mice: potential application in occupational toxicology?

Abstract

Since the nephrotoxic effects of the cysteine conjugate of trichloroethylene, dichlorovinyl cysteine (DCVC), was discovered, a number of additional toxic conjugates of halogenated alkenes have been found [e.g. Ref. 11. Using DCVC as model compound, studies on its accumulation in mice, and the conditions for renal binding and toxicity, have been performed [2,3]. In order to validate a non-invasive method of monitoring the DCVC-induced kidney lesion, selected renal enzymes were quantified in the urine of treated mice. The results were compared with those from blood urea nitrogen (BUN) measurements. Clinical applications of the results are discussed. Commercial kits for the determination of y-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) (if necessary modified to fit urinary measurements), and of BUN, were used (all from Sigma Chem. Co., St. Louis, MO, U.S.A.). Mice (female C57BL) were treated with DCVC in groups of 4 (see Table I). Twenty-four hours after the oral administration, the urine was collected, centrifuged, and kept at 4°C until analysis. The animals were killed and the kidneys were taken out for histopathological examination (paraffin sections, H-E staining). The results from the urinary enzyme (total activity/24 h + SD) and BUN measurements on DCVC-treated mice are presented in Table I. The GGT and LDH values