H. Maling, F. Eichelbaum, W. Saul
May 15, 1974
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0
Influential Citations
59
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Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract In this paper, we assess various plausible mechanisms by which pretreatment with Dibenamine [ N -(2-chloroethyl) dibenzylamine] hydrochloride (25 mg/kg, s.c., 48 and 24 hr before the administration of CCl 4 ) protects rats against the hepatotoxic effects of CCl 4 . Dibenamine pretreatment did not affect significantly the absorption of CCl 4 after i.p. administration or the elimination of CCl 4 from various tissues, as evident from unchanged tissue levels. Dibenamine pretreatment decreased the accumulation of the metabolite CHCl 3 in liver, the isopropanol-potentiated covalent binding of a small dose of 14 CCl 4 (0.1 ml/kg) and the covalent binding of a necrosis-producing dose of 14 CCl 4 (1.0 ml/kg) to proteins and lipids in liver, and the diene conjugation of liver microsomal lipids induced by CCl 4 . These findings suggest that Dibenamine pretreatment impairs the microsomal enzymes which catalyze the formation of free radical derivatives of CCl 4 . Dibenamine protection is not correlated with its concentration in liver or with the covalent binding of Dibenamine derivatives to liver microsomal protein.