Effects of N-(2-propylpentanoyl) urea on rat hepatic cytochrome P450 and glutathione S-transferase

Abstract

Effects of N-(2-propylpentanoyl) urea (VPU) on rat hepatic cytochrome P450, glutathione S-transferase and total glutathione were investigated. VPU and valproic acid (VPA) were given intraperitoneally to male Wistar rats at a dosage of 80 and 250 mg/kg. respectively, once daily for 7 days. On the day after, the animals were sacrificed by cervical dislocation and the livers were prepared for microsomal and cytosolic subfractions. Microsomal total cytochrome P450 contents and the enzyme activities, cytosolic glutathione S-transferase activities as well as hepatic total glutathione contents were determined. No effects of VPU and VPA were observed on total cytochrome P450 contents, ethoxy- and methoxyresorufin o-dealkylase activities (representing CYP1A1 & CyP1A2 activities), aniline 4-hydroxylase activities (representing CYP2E1 activities), glutathione S-transferase activities and hepatic total glutathione contents. However, benzyloxy- and pentoxyresorufin o-dealkylase activities (representing CYP2B1 & CYP2B2 activities) were significantly increased by VPU, correspondingly to a slight increase of CYP2B1 & CYP2B2 proteins detected by Western blotting. Further study to clarify the mechanism of this enzyme induction should be proceeded. Moreover, various doses and extended duration of VPU administrations should be additionally studies. Effect of VPU on other isoforms of CYP, involving human drug metabolism, was also suggested exploring.