In vitro and in vivo nephrotoxicity of the L and D isomers of S-(1,2-dichlorovinyl)-cysteine.
The toxicity of the optical isomers S-(1,2-dichlorovinyl)-L-cysteine (L-DCVC) and S-(1,2-dichlorovinyl)-D-cysteine (D-DCVC) was investigated in vivo and in vitro. In vitro studies, utilizing a rabbit renal cortical slice system, demonstrated toxicity due to both forms with the L-form being more toxic. Dose- and time-dependent decreases in intracellular K+ and LDH were observed. Both compounds produced an initial S3 lesion, L-DCVC at 10(-5) M (12 h), D-DCVC at 10(-4) M (8 h), followed by a lesion encompassing all proximal tubules. In vivo studies demonstrated elevated blood urea nitrogen values at 24 and 48 h with 25 mg/kg of either isomer. Histopathology indicated both D and L-DCVC produced a straight proximal tubular lesion by 48 h, the lesion produced by L-DCVC being more severe. The D and L isomers of DCVC were both shown to be toxic, the toxicity assessed in vitro corresponded well with the toxicity in vivo.
Wolfgang
G H
GH
Department of Pharmacology and Toxicology, University of Arizona, Tucson 85724.
Gandolfi
A J
AJ
Stevens
J L
JL
Brendel
K
K
D000818:Animals; D001806:Blood Urea Nitrogen; D046508:Culture Techniques; D003545:Cysteine / Q000633:toxicity / Q000031:analogs & derivatives; D007536:Isomerism; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
C039961:S-(1,2-dichlorovinyl)cysteine; D007770:L-Lactate Dehydrogenase; D003545:Cysteine; D011188:Potassium