Effect of N-(2-Propylpentanoyl) Urea on Rat Hepatic Drug Metabolizing Enzymes

Abstract

Effect of N-(2-propylpentanoyl)urea (VPU) on rat hepatic drug metabolizing enzymes wasinvestigated. Median effective dose of VPU as well as that of valproicacid (VPA, the prototype of VPU) were given intraperitoneally to male Wistar rats for 7 days. On the day after, the animals were sacrificed by cervical dislocation. Hepatic microsomal and cytosolic subfractions were isolated.Microsomal total cytochrome P450 contents, microsomal cytochrome P450 enzyme-substrateactivities, cytosolic glutathione S-transferase activities and hepatic total glutathione were determined. No effects of VPU and VPA were observed on total cytochrome P450 contents, ethoxy- andmethoxyresorufin 0-dealkylase activities (representing CYP 1A1&1A2 activities), aniline 4-hydroxylase activities (representing CYP 2E1 activities), glutathione S-transferase activities andhepatic total glutathione. However, pentoxy- and benzyloxyresorufin 0-dealkylase activities(representing CYP 2B1&2B2 activities) were significantly increased by VPU. Correspondingly, CYP2B1&2B2 proteins detected by Western blotting were slightly increased following VPU treatment. Further study on the effect of VPU on other isoforms of CYP, involving in human drug metabolism, was suggested.