Changes of Drug Metabolizing Enzymes in the Liver of Male Sheep Exposed to either Cypermethrin or Dimethoate

S. A. Sheweita, M. I. Yousef, H. H. Baghdadi, A. G. Elshemy

Abstract

Xenobiotics such as insecticides are metabolized to more or less toxic metabolites by drug-metabolizing enzymes including cytochrome P450 (Cyp P450), cytochrome b5 (Cyp b5), NADPH-cytochrome c reductase (Cyt.c R), N-nitrosdimethylamine-N-demethylase I (NDMA-dI), glutathione (GSH), glutathione s-transferase (GST), and glutathione reductase (GR). Therefore, the present study showed the influence of oral administration of cypermethrin (6 and 12 mg/kg/day) and dimethoate (1.6 and 3.2 mg/kg/day) for 63 consecutive days on the activities of the above mentioned enzymes in the livers of male sheep. Low and high-treatments of sheep with cypermethrin significantly increased the levels of Cyp P450 by 56% and 98%, Cyp b5 by 65% and 80%, GSH by 68% and 74%, and Cyt.c R by 67% and 98%, respectively in a dose-dependent manner. However, low dose of cypermethrin increased the activities of GST and GR by 56% and 91% respectively. In addition, low and high dose-treatments with dimethoate increased the hepatic contents of Cyp P450 by 27% and 40%, GSH by 259% and 132%, whereas NDMA-dI decreased by 27 and 55% respectively, and no change in the content of Cyp b5 and the activity of Cyt.c-R at any given dose of this compound. It is concluded that exposure to cypermethrin and dimethoate significantly changed the hepatic activity of phases I & II drugmetabolizing enzymes in sheep, and these changes are mainly dependent on the administred dose, and also on the type of the tested insecticides. Also, such changes should be considered when therapeutic drugs administered to people exposed to such insecticides.

Keywords: Drug Metabolizing Enzymes, Liver, Cypermethrin, Dimethoate, Insecticides, Cytochrome P450, glutathione s-transferase, pyrethroid pesticides, Organophosphorus, xenobiotic-metabolizing enzymes