Prevention of carbon tetrachloride-induced liver necrosis by the chelator alizarin sodium sulfonate.
The administration of the calcium chelator alizarin sodium sulfonate (ASR) (100 mg/kg ip in saline) 30 min before or 6 or 10 hr after CCl4 (1 ml/kg ip as a 20% v/v solution in olive oil) partially prevents the necrogenic effect of the hepatotoxin at 24 hr, but prevention of CCl4 fat accumulation was not observed. Protective action cannot be attributed to potential decreasing effects of ASR on CCl4 levels reaching the liver, on the covalent binding of CCl4-reactive metabolites to cellular components, or on CCl4-induced lipid peroxidation because ASR does not modify these parameters significantly. ASR administration increases GSH levels in livers of both control and CCl4-poisoned animals and decreases the calcium content of intoxicated animals at 24 hr of poisoning. ASR significantly lowers the body temperature of CCl4-treated animals at different times of the intoxication process. Present and previous results from our laboratory on the preventive effects of another very specific calcium chelator, calcion, and several anticalmodulins suggest that the beneficial effects of ASR might be associated with its calcium chelating ability. Other protective effects of ASR, such as lowering body temperature or increasing GSH content in liver, cannot be excluded.
de Ferreyra
E C
EC
Centro de Investigaciones Toxicológicas (CEITOX), CITEFA/CONICET, Villa Martelli Provincia de Buenos Aires, Argentina.
Villarruel
M C
MC
Bernacchi
A S
AS
de Fenos
O M
OM
Castro
J A
JA
D000818:Animals; D000880:Anthraquinones / Q000097:blood / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002251:Carbon Tetrachloride / Q000009:adverse effects* / Q000032:analysis / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000032:analysis; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009336:Necrosis; D011485:Protein Binding; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000880:Anthraquinones; D002614:Chelating Agents; D008055:Lipids; D011506:Proteins; C004468:Alizarin Red S; D002251:Carbon Tetrachloride; D005978:Glutathione; D002118:Calcium