Acta Physiologica 79. (1992)

1. szám - PHYSIOLOGY-PATHOPHYSIOLOGY - Ildikó Szabó-Á. Vas-G. Renczes: Effect of flumecinol (Zixoryn) on the cytochrome P450 and cytochrome P448 dependent hepatic microsomal monooxygenase activities in male rats

Acta Physiologica Hungarica, Volume 79 (1), pp. 23 - 27 (1992) EFFECT OF FLUMECINOL (ZIXORYN) ON THE CYTOCHROME P450 AND CYTOCHROME P44g DEPENDENT HEPATIC MICROSOMAL MONOOXYGENASE ACTIVITIES IN MALE RATS Ildikó Szabó, Á. Vas*, G. Renczes* APÁTHY ISTVÁN CHILDRENS HOSPITAL, BUDAPEST •POSTGRADUATE MEDICAL UNIVERSITY, I. DEPARTMENT OF MEDICINE, DIVISION OF CLINICAL PHARMACOLOGY, BUDAPEST, HUNGARY Received November 14, 1990 Accepted December 11,1991 The effect of three-day oral administration of 50 mg/kg bw. and 100 mg/kg bw. flumecinol (Zixoryn, Gedeon Richter Chemical Works Ltd., Budapest, Hungary) and intraperitoneal administration of 50 mg/kg bw. phénobarbital as well as the single intraperitoneal administration of 20 mg/kg bw. 3-methylcholanthrene on various cytochrome P450 and P448 dependent hepatic microsomal enzyme activities was studied in male albino Wistar rats. 50 mg/kg bw. flumecinol had no significant effect. 100 mg/kg bw. flumecinol had an inducing effect comparable to the one of phénobarbital. The activity of the cytochrome P448 dependent 7-ethoxyresorufin O-deethylase was enhanced by all three substances, but flumecinol’s effect was by far behind that of 3-methylcholanthrene, so the carcinogenic promoter effect of flumecinol can be questioned. Keywords: flumecinol, microsomal enzyme activities, ratsi The metabolism of xenobiotics may lead to the generation of toxic, potentially carcinogenic intermediers [4]. The cytochrome P450 dependent hepatic microsomal polysubstrate monooxygenase system plays thus a key role not only in the detoxification of various agents but also in the generation of toxic metabolites. Cytochrome P448 activity is closely linked to the generation of carcinogenic metabolites [11]. The cytochrome P448 content of tumor tissues is high and the increase of it is an early indicator of malignant transformations [14]. All xenobiotics with inducing effect on cytochrome P448 content and/or activity are considered Correspondence should be addressed to Ildikó Szabó Apáthy István Childrens Hospital H-1046 Budapest, Bethesda u. 3, Hungary

Next