Title: Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs Zhuang Z, Tang M, Zheng Y, Hu L, Lin F Ref: Pharmacology, 95:243, 2015 : PubMed
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-infinity), 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. (c) 2015 S. Karger AG, Basel.
        
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Zhuang Z, Tang M, Zheng Y, Hu L, Lin F (2015) Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs Pharmacology95: 243-250
Zhuang Z, Tang M, Zheng Y, Hu L, Lin F (2015) Pharmacology95: 243-250