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Imipramine prevention of carbon tetrachloride‐induced liver necrosis at late states of the intoxication process
Author(s) -
Fernández G.,
Villarruel M. C.,
de Ferreyra E. C.,
de Fenos O. M.,
Castro J. A.
Publication year - 1986
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550060606
Subject(s) - hepatotoxin , chemistry , imipramine , carbon tetrachloride , microsome , lipid peroxidation , pharmacology , cytochrome , toxicity , endocrinology , phospholipid , medicine , biochemistry , antioxidant , in vitro , enzyme , alternative medicine , organic chemistry , pathology , membrane
Impiramine administration (50 mg kg −1 , i.p.) to Sprague–Dawley male rats (240–290 g) 6 or 10 h after CCl 4 (1 ml kg −1 , i.p.) partially prevents liver necrosis induced by the hepatotoxin. When imipramine is given 30 min before CCl 4 , it inhibits in part the CCl 4 ‐inhibits in part the CCl 4 ‐induced lipid peroxidation and the covalent interactions of reactive metabolites with microsomal lipids or proteins and partially prevents CCl 4 ‐induced cytochrome P‐450 destruction, but not glucose 6 phosphatase activity depression. Impiramine administration prior to CCl 4 does not modify levels of the hepatotoxin reaching the liver or the body temperature of CCl 4 treated animals. Early preventive effects of imipramine on cytochrome P‐450, might be attributed to inhibition of covalent interactions of reactive metabolites. The hypothesis that imipramine exerted late preventive effects by interfering with calcium deleterious effects or by modulation of protein and phospholipid synthesis or degradation is analyzed.