The acute effects of S-(1,2-dichlorovinyl)-L-cysteine and related chemicals on renal function and ultrastructure in the pentobarbital-anesthetized dog: structure-activity relationships, biotransformation, and unique site-specific nephrotoxicity.

S-(1,2-Dichlorovinyl)-L-cysteine (L-DCVC), a substrate for the renal cysteine conjugate beta-lyase, and other related chemicals were administered intravenously to pentobarbital-anesthetized dogs. Six pertinent findings emerged regarding their nephrotoxicity. (1) L-DCVC was acutely nephrotoxic in the dog. (2) The earliest indicator of L-DCVC-induced renal damage was an increase in the urinary excretion rate of protein. (3) Contrary to results from other species, L-DCVC induced renal ultrastructural lesions only in the S1 and S2 cells of the proximal tubule. (4) The toxicity of L-DCVC (23.15 mumol/kg, iv) to S1 and S2 cells resulted from a direct tubular insult and not from overlapping episodes of hypoxia or ischemia. (5) L-DCVC could be detected in plasma only during the first 30 min after its injection. In addition, no L-DCVC and only small amounts of N-acetyl-L-DCVC and S-(1,2-dichlorovinyl)mercaptoacetic acid (DCV-MAA) (1.5% and less than 1% of the administered dose, respectively) were detectable in urine during the 6 hr following L-DCVC administration. (6) DCV-MAA and chloroacetic acid as well as other compounds that are not substrates for the renal cysteine conjugate beta-lyase (i.e., S-allyl-L-cysteine, vinthionine, and S-(1,2-dichlorovinyl)-D,L-alpha-methylcysteine) were not acutely nephrotoxic. These findings provide indirect evidence for the involvement of beta-lyase in the toxification of L-DCVC in the dog.