TY - JOUR
T1 - In vitro and in vivo nephrotoxicity of the L and D isomers of S-(1,2-dichlorovinyl)-cysteine
AU - Wolfgang, Grushenka H.I.
AU - Jay Gandolfi, A.
AU - Stevens, James L.
AU - Brendel, Klaus
N1 - Funding Information: This research was supported by NIH Grants DK 38925 and GM 38290, Training Grant T32 ES 07091, and Johns Hopkins Center for Alternatives to Animal Testing. We thank Patricia Kime for typing the manuscript.
PY - 1989/9
Y1 - 1989/9
N2 - 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.
AB - 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.
KW - 1,2-Dichlorovinyl cysteine (D,L forms)
KW - Culture slices (renal)
KW - Renal (in vivo)
KW - Renal slices
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U2 - 10.1016/0300-483X(89)90102-9
DO - 10.1016/0300-483X(89)90102-9
M3 - Article
C2 - 2815092
SN - 0300-483X
VL - 58
SP - 33
EP - 42
JO - Toxicology
JF - Toxicology
IS - 1
ER -