Late preventive effects against carbon tetrachloride-induced liver necrosis of the calcium chelating agent Calcion.
In agreement with the hypothesis that changes in calcium homeostasis might be significant in late stages of chemically-induced liver cell injury, a calcium chelating agent, Calcion, was able to partially prevent CCl4-induced liver necrosis observed at 24 h, when treatment was given as late as 6 or 10 h after the hepatotoxin. Calcion had minor or no effects on covalent binding of reactive metabolites to cellular components, or on lipid peroxidation or on CCl4 levels reaching the liver. Calcion treatment of CCl4-poisoned animals decreased CCl4-induced calcium increases in liver and increased glutathione levels decreased by hepatotoxin at 24 h. Calcion treatment was not able to prevent CCl4-induced fatty liver. Calcion protective effects were body temperature dependent but they were cancelled when Calcion-treated poisoned animals were kept normothermic. Results suggest that Calcion protective effects might be linked to calcium chelation or alternatively that they might derive from decreases in body temperature.
de Ferreyra
E C
EC
Centro de Investigaciones Toxicológicas, (CEITOX) CITEFA/CONICET, Buenos Aires, Argentina.
Villarruel
M C
MC
Bernacchi
A S
AS
Fernández
G
G
de Fenos
O M
OM
Castro
J A
JA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control; D002614:Chelating Agents / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000378:metabolism; D006651:Histocytochemistry; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009282:Naphthalenesulfonates / Q000627:therapeutic use*; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains
D002614:Chelating Agents; D009282:Naphthalenesulfonates; C062797:Calcion; D002251:Carbon Tetrachloride; D005978:Glutathione; D002118:Calcium