title: Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs.
abstract: BACKGROUND
  Dimethoate (DM), one of the most widely used systemic organophosphate insecticide, has been reported to exert toxic effects after long-time subchronic exposure. This study aims at investigating the toxic effect of DM on liver after repeated administration of low doses of DM in rats.
  
  
  METHODS
  Twenty Sprague-Dawley rats were randomly divided into the control group (n = 10) and the DM group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were evaluated by the Cocktail method.
  
  
  RESULTS
  The level of AChE (acetylcholinesterase) was significantly decreased, hepatic functions were damaged and the mRNA level of CYP2D1 was significantly increased in the DM group (p < 0.05). The pharmacokinetics of probe drug revealed AUC(0-t), AUC(0-∞), t1/2 and Cmax of metoprolol was shorten in the DM group (p < 0.05). However, there were no statistical differences in MRT, t1/2, CL and Tmax for phenacetin, tolbutamide and midazolam.
  
  
  CONCLUSIONS
  A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks.
authors.affiliation: Department of Intensive Care Unit, Cangnan People's Hospital, Lingxi Town, Cangnan County, Wenzhou, Zhejiang, China.
authors.forename: Zaishou
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Tang
authors.forename: Yangming
authors.initials: Y
authors.lastname: Zheng
authors.forename: Lufeng
authors.initials: L
authors.lastname: Hu
authors.forename: Feiyan
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004117:Dimethoate / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics*; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D010615:Phenacetin / Q000097:blood / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D010615:Phenacetin; D008790:Metoprolol; D008874:Midazolam; D004117:Dimethoate