title: Late preventive effects of quinacrine on carbon tetrachloride induced liver necrosis.
abstract: We have previously reported that treatments stimulating phospholipid (PL) synthesis or preventing PL degradation were late preventive agents against CCl4-induced liver necrosis. Later studies by others postulated that stimulation of phospholipase A2 (PLA2) plays a role in PL degradative processes responsible for CCl4 damage. Quinacrine (QUIN) is a well known inhibitor of PLA2. In this work we report that QUIN (150 mg/kg i.p.) partially prevents CCl4-induced liver necrosis at 24 h when given 30 min before or 6 or 10 h after CCl4 (2.5 ml/kg p.o.) QUIN administration does not modify at 1 or 3 h after poisoning CCl4 levels reaching the liver, covalent binding of CCl4 reactive metabolites to proteins or lipids, CCl4-induced lipid peroxidation process, CCl4-induced decreases in body temperature, or glutathione levels in liver. QUIN concentrations in liver at times from 1 to 24 h are well over those required to inhibit PLA2 activity. Results are compatible with the hypothesis that CCl4 activation of PLA2 at late stages of poisoning plays a role in CCl4-induced liver necrosis.
authors.affiliation: Centro de Investigaciones Toxicológicas (CEITOX) CITEFA/CONICET, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: González Padrón
authors.forename: E G
authors.initials: EG
authors.lastname: de Toranzo
authors.forename: J A
authors.initials: JA
authors.lastname: Castro
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002250:Carbon Radioisotopes; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000378:metabolism; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011796:Quinacrine / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D010743:Phospholipids; D011506:Proteins; D002251:Carbon Tetrachloride; D010741:Phospholipases A; D054467:Phospholipases A2; D005978:Glutathione; D011796:Quinacrine; D002118:Calcium