Possible role of metal redistribution, hepatotoxicity and oxidative stress in chelating agents induced hepatic and renal metallothionein in rats.
A study was planned to investigate possible role of oxidative stress, hepato- and nephrotoxicity and essential metal redistribution following administration of amino and thiol chelating agents on hepatic and renal metallothionein (MT) and the levels of some metalloenzymes in male rats. Animals were administered 50 mg/kg, intraperitoneally, twice daily for 15 consecutive days; a dose of three amino and four thiol chelators and were sacrificed 24 h after the last dose. The results indicate no evidence of oxidative stress in hepatic and renal tissues of rats administered thiol and amino chelators, except for some marginal changes in the animals treated with calcium disodium ethylenediaminetetraacetic acid (EDTA) and D-penicillamine (DPA). Redistribution of essential metal (particularly zinc), hepato- and nephrotoxicity seems to play a significant role in influencing the MT induction by amino chelators. Redistribution of essential metals may also be playing a significant role in a number of metalloenzymes, especially by amino chelators compared to thiol chelators. It can thus be concluded that toxic effects of chelating agents, including metal redistribution and hepatotoxicity, might be playing a crucial role in the metallothionein induction.
Mehta
A
A
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474 002, India.
Flora
S J
SJ
D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008668:Metallothionein / Q000096:biosynthesis*; D008670:Metals / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002614:Chelating Agents; D008670:Metals; D011524:Protoporphyrins; D008315:Malondialdehyde; D008668:Metallothionein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000623:Porphobilinogen Synthase; D005978:Glutathione