Effect of monoisoamyl meso-2,3-dimercaptosuccinate on the pathology of acute cadmium intoxication.
The ability of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) to offset the characteristic organ pathology of intraperitoneally administered cadmium chloride (CdCl2) and that of the cadmium-cysteine complex has been examined in male Wistar rats. The tissues examined for damage were the testes, kidney, liver, pancreas, and bone marrow. At a high dose of CdCl2 (0.03 mmol/kg, ip) testicular damage was completely prevented by Mi-ADMS (0.50 mmol/kg, ip) given immediately. A decrease in the protective ability of the antagonist was observed following delayed administration of Mi-ADMS given at 1, 2, 4, and 24 h post CdCl2. At a lower dose of CdCl2 (0.006 mmol/kg, ip), Mi-ADMS furnished essentially full protection from testicular damage when given (0.50 mmol/kg, sc) at 0 and 1 h after CdCl2. The administration of cadmium-cysteine complex (0.01 mmol/kg, ip) induced notable renal tubular damage, which was antagonized by the administration of Mi-ADMS (0.50 mmol/kg, ip) as late as 4 h after the complex. At a 24-h delay, extensive tubular necrosis was found on sacrifice after 4 d. The administration of cadmium-cysteine complex ip reduced, but did not eliminate, the characteristic damage of the seminiferous tubules found for cadmium alone. There is a progressive reduction of testicular weight as the interval between cadmium and antagonist administration increases. The average kidney weights of the animals given CdCl2-cysteine complex were increased in comparison to normal controls. The antagonistic effects of Mi-ADMS treatment on cadmium intoxication in the kidneys and the testes of rats is very similar to that found for effective dithiocarbamate antagonists. In order to obtain complete protection of the testes from the deteterious effects of cadmium, such antagonists must be administered no later than about 1 h after the cadmium.
Xu
C
C
Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 87235, USA.
Holscher
M A
MA
Jones
M M
MM
Singh
P K
PK
D000208:Acute Disease; D000818:Animals; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D019256:Cadmium Chloride; D002614:Chelating Agents / Q000494:pharmacology*; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003545:Cysteine / Q000633:toxicity; D004338:Drug Combinations; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000031:analogs & derivatives* / Q000494:pharmacology; D013737:Testis / Q000187:drug effects* / Q000473:pathology
D002614:Chelating Agents; D002712:Chlorides; D004338:Drug Combinations; D002104:Cadmium; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D019256:Cadmium Chloride; D003545:Cysteine