Evaluation of chelating drugs on the toxicity, excretion, and distribution of nickel in poisoned rats.
The effects of various doses of two macrocyclic drugs, namely, 1,4,8,11-tetraazacyclotetradecane (Cyclam) and 5,7,7',12,14,14'-hexamethyl-1,4,8,11-tetraazacyclotetradecane++ + (Cyclam s), on the toxicity, distribution, and excretion of nickel were evaluated in nickel-poisoned rats and compared with the linear counterpart triethylenetetraamine (TETA) and a tripeptide, glutathione (GSH). Cyclam and Cyclam s revealed a higher order of efficacy against the lethal response of nickel even at a lower dose. These drugs significantly enhanced the urinary and biliary excretion of nickel and restored the altered levels of trace metals (viz., Cu, Zn, Fe, Mn) compared to TETA and GSH. The efficacy of these drugs in vivo may be related to their ability to transport nickel across an artificial lipid membrane, a phenomenon was not exhibited by TETA or GSH.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D009532:Nickel / Q000378:metabolism* / Q000506:poisoning; D051381:Rats; D014018:Tissue Distribution; D014266:Trientine / Q000494:pharmacology
D002614:Chelating Agents; D006571:Heterocyclic Compounds; C024560:cyclam; D009532:Nickel; D005978:Glutathione; D014266:Trientine