Protective effects of thiol containing chelating agents against liver injury induced by hexavalent chromium in mice.
The effects of the chelating agents, L-cysteine ethyl ester (LCEE), L-cysteine methyl ester (LCME), N-acetyl-L-(+)-cysteine (NAC), 2,3-dimercapto-1-propanesulfonic acid (DMPS), N-(2-mercaptopropionyl)-glycine (MPG), and 2,3-dimercaptosuccinic acid (DMSA), on the distribution, excretion and hepatotoxicity of ip injected hexavalent chromium were studied in male mice. The chelating agents (500 mg/kg) were injected iv as single doses given immediately or 30 min after potassium dichromate (20 mg Cr/kg) as hexavalent chromium was administered. When the chelating agents were injected immediately after the metal compound was administered, LCEE, LCME, NAC, DMPS, and MPG reduced the chromium contents in the liver and kidney, and facilitated the urinary excretion of chromium. The liver injury induced by chromium, which was evaluated by serum ornithine carbamyl transferase (OCT) activity, was prevented significantly by LCEE, LCME, DMPS, and MPG. On the other hand, when these chelating agents were injected at 30 min after the chromium administration, only DMSA could prevent the liver injury induced by the metal, and decreased the chromium contents in the liver. However, when DMSA was given at 3 hr after the metal administration, there was no therapeutic effect on them. These results suggest that the chelating agents tested may be useful in the treatment of intoxications due to hexavalent chromium, but there is the difference in the therapeutic effects of the chelating agents owing to the time intervals after the administration of the metal.
Ueno
S
S
Department of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Aomori, Japan.
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D002840:Chromates / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D004113:Succimer / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D002614:Chelating Agents; D002840:Chromates; D013438:Sulfhydryl Compounds; D004113:Succimer