Effects of several pyrethroids on hepatic cytochrome P450 activities in rats. 2010

Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology.

Four commonly used pyrethroids (permethrin, bifenthrin, ethofenprox, and fenpropathrin) were orally administered to Sprague-Dawley rats for 5 days to study their effects on the liver cytochrome P450 (CYP) activities. Also Michaelis-Menten kinetics of the metabolic reactions catalyzed by liver CYPs were examined after adding these pyrethroids to the assay system to investigate their possible inhibitory effects on liver CYPs activities. These reactions included ethoxyresorufin O-deethylation, tolbutamide hydroxylation, bufuralol 1'-hydroxylation, and midazolam 4-hydroxylation, for CYP1A, 2C, 2D, and 3A activities, respectively. Results showed that oral administration of bifenthrin and ethofenprox highly induced CYP1A. The most potent inhibitors for CYP1A were fenpropathrin and cis-permethrin with K(i) values of 3.71 & 3.87 microM, respectively. CYP2D was slightly inhibited by both of fenpropathrin and cis-permethrin (K(i) values were 307.32 & 632.23 microM, respectively). On the other hand, none of CYP2C or 3A was inhibited by the tested pyrethroids. Since CYP1A may relate to biotransformation of many chemicals to reactive metabolites, bifenthrin and ethofenprox may potentiate mutagenicity of the chemicals through their inducing effects on CYP 1A. As permethrin and fenpropathrin were potent inhibitor for CYP1A, they may result in substantial accumulation of some chemicals. The resultant accumulation may lead to fatal toxicities in some case.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D011722 Pyrethrins The active insecticidal constituent of CHRYSANTHEMUM CINERARIIFOLIUM flowers. Pyrethrin I is the pyretholone ester of chrysanthemummonocarboxylic acid and pyrethrin II is the pyretholone ester of chrysanthemumdicarboxylic acid monomethyl ester. Pyrethrin,Pyrethroid,Pyrethroids
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

Related Publications

Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
September 1998, Xenobiotica; the fate of foreign compounds in biological systems,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
April 1993, Anesthesia and analgesia,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
January 2018, Biological & pharmaceutical bulletin,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
February 1992, Biochemical pharmacology,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
June 1995, Xenobiotica; the fate of foreign compounds in biological systems,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
February 2002, Drug and chemical toxicology,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
January 1992, Acta physiologica Hungarica,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
March 1994, Canadian journal of physiology and pharmacology,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
July 2018, International journal of molecular sciences,
Rania Abdou, and Kazuaki Sasaki, and Waleed Khalil, and Syed Shah, and Youhei Murasawa, and Minoru Shimoda
November 1995, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.),
Copied contents to your clipboard!