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Relation between hepatic and renal function tests and ultrastructural changes induced by 2-N-methylpiperazinomethyl-1,3-diazafluoranthen 1-oxide (AC-3579), a new experimental antileukemic drug

par Ghys, A.;Thys, Olivier ;Hildebrand, Jerzy ;Georges, A.
Référence Toxicology and applied pharmacology, 31, 1, page (13-20)
Publication Publié, 1975-01

Article révisé par les pairs

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Résumé :

The toxicity of 2-N-methylpiperazinomethyl-1,3-diazafluoranthen 1-oxide (AC-3579, NSC-170561) was investigated in Sprague-Dawley rats. The drug was administered po at a daily dose of 500 mg/kg for 30 days. The drug reduced feed intake, lowered average body weight, and produced a marked increase in liver weight. Ultrastructural study of hepatocytes showed an increase of smooth endoplasmic reticulum and the presence of numerous lysosomes overloaded with lamellar material. Lamellate cytosomes were also seen in kidney convoluted tubule cells. In contrast with the striking morphologic alterations observed in hepatocytes, the results of tests of hepatic function performed at the end of the treatment did not differ markedly from controls except for a 42-fold increase in the activity of γ-glutamyl-transpeptidase and a mild increase in the activities of ornithine carbamyl transferase and glutamic pyruvic transaminase. Urea nitrogen was elevated slightly, but creatinine and uric acid were similar for test and control animals. There was practically no effect on blood elements. Most of the observed changes were reversible. © 1975.