Chelation in metal intoxication: influence of cysteine or N-acetyl cysteine on the efficacy of 2,3-dimercaptopropane-1-sulphonate in the treatment of cadmium toxicity.
The influence of cysteine or N-acetyl cysteine administration on the efficacy of 2,3-dimercaptopropane-1-sulphonate (DMPS) in the treatment of cadmium intoxication was investigated in cadmium-pre-exposed rats. Cysteine, N-acetyl cysteine, DMPS, DMPS + cysteine or DMPS + N-acetyl cysteine were about equal in effectiveness in mobilizing hepatic cadmium mainly from its supernatant cytosolic fraction (SCF) and both of the combinations were more effective than either of them alone in mobilizing cadmium from its nuclear mitochondrial fraction (NMF). The DMPS was apparently more effective than cysteine or N-acetyl cysteine in mobilizing renal cadmium from its SCF or NMF and it was more effective than even their combinations in mobilizing cadmium from renal SCF. The treatment with cysteine or N-acetyl cysteine reduced cadmium-induced hepatic and renal metallothionein (MT) and the treatment with DMPS reduced renal MT only, probably due to removal of hepatic and renal SCF cadmium by these agents. However, MT levels were high in animals treated with DMPS + cysteine or DMPS + N-acetyl cysteine, despite lowering of cadmium in these tissues, suggesting a contribution of MT induced by cysteine or N-acetyl cysteine itself. The cadmium exposure increased hepatic and renal zinc and renal copper levels, probably as a result of cadmium-induced MT, and some of the levels were normalized considerably by the subsequent treatment with cysteine, DMPS or to a lesser extent N-acetyl cysteine and their combinations, showing their protective effects against cadmium toxicity. The increase in blood cadmium and the decrease in blood zinc and copper levels due to cadmium exposure also were reversed appreciably by some of these treatments. The results have shown a limited benefit of cysteine or N-acetyl cysteine administration on the efficacy of DMPS in the treatment of cadmium intoxication.
Tandon
Sushil K
SK
Chemical Toxicology, Industrial Toxicology Research Centre, Lucknow, India. sktandon19@yahoo.com
Prasad
Satgur
S
Singh
Surendra
S
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000097:blood / Q000633:toxicity*; D002614:Chelating Agents / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008668:Metallothionein / Q000032:analysis; D051381:Rats; D016896:Treatment Outcome; D014494:Unithiol / Q000494:pharmacology*
D002614:Chelating Agents; D002104:Cadmium; D014494:Unithiol; D008668:Metallothionein; D003545:Cysteine; D000111:Acetylcysteine