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Journal of Pharmacology And Experimental Therapeutics, Vol. 186, Issue 3, 416-424, 1973
Copyright © 1973 by American Society for Pharmacology and Experimental Therapeutics

EFFECTS OF HYCANTHONE AND TWO OF ITS CHLORINATED ANALOGS ON HEPATIC MICROSOMES

G. W. LUCIER 1, O. S. McDANIEL 1, J. R. BEND 1, and E. FAEDER 1

1 National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health, Education, and Welfare, Research Triangle Park, North Carolina

Recent reports have demonstrated that the antischistosomal drug hycanthone can have mutagenic, teratogenic and hepatotoxic properties. In this study, the effects on hepatic microsomes were investigated after a single i.m. injection of hycanthone or two of its chlorinated analogs to male rats. Two days after treatment with 100 mg/kg of hycanthone, aminopyrine demethylation was decreased by 48% and cytochrome P-450 by 34%. Aminopyrine demethylation remained approximately 50% of control values through the 7th day after hycanthone injection. Enzyme activity returned to control levels by the 14th day. Microsomal protein was decreased by hycanthone treatment and this was attributable to decreased smooth endoplasmic reticulum protein. Effects of hycanthone on other microsomal enzymes such as glucuronyltransferase, beta-glucuronidase and acid phosphatase were not as great as those observed on the mixed function oxidase components. IA-4 (6-chloroindazole analog of hycanthone) did not markedly affect any of the microsomal parameters tested, whereas IA-3 (6-chloroindazole analog of lucanthone) decreased aminopyrine demethylation by 38% in smooth endoplasmic reticulum. Dose-response studies demonstrated that aminopyrine demethylation and cytochrome P-450 were significantly decreased by a single hycanthone injection at 50 or 100 mg/kg. A dose of 25 mg/kg caused only slight decreases in these parameters.

Submitted on February 13, 1973
Accepted on May 10, 1973




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P. B. Hulbert, P. E. Hartman, and E. Bueding
Hycanthone Analogs: Dissociation of Mutagenic Effects from Antischistosomal Effects
Science, November 15, 1974; 186(4164): 647 - 648.
[Abstract] [PDF]


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Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics.