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. 2015 Oct 15;8(10):19100-6.
eCollection 2015.

Effect of acute paraquat poisoning on CYP450 isoforms activity in rats by cocktail method

Shuanghu Wang  1 , Zhiyi Wang  2 , Dongxin Chen  3 , Mengchun Chen  2 , Yingying Lin  3 , Zezheng Liu  3 , Lijing Zhang  3 , Congcong Wen  3 , Xianqin Wang  3 , Jianshe Ma  4
Affiliations

Effect of acute paraquat poisoning on CYP450 isoforms activity in rats by cocktail method

Shuanghu Wang et al. Int J Clin Exp Med. .

Abstract

Paraquat is a highly effective contact herbicide that is marketed worldwide as a fantastical, non-selective compound for broadleaf weed control. As compared to most pesticides, paraquat is extremely toxic to humans and the lack of strategies to manage paraquat poisoning has resulted in high fatality rates. The rats were randomly divided into acute paraquat poisoning group and control group. The paraquat group rats were given 36 mg/kg paraquat by intragastric administration. The influence of acute paraquat poisoning on the activities of CYP450 isoforms CYP2B6, CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19 were evaluated by cocktail method, they were responded by the changes of pharmacokinetic parameters of bupropion, phenacetin, tolbutamide, metoprolol, midazolam and omeprazole. The six probe drugs were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. In the results of paraquat group compared to control group, there was statistical pharmacokinetic difference for bupropion, tolbutamide, metoprolol, midazolam and omeprazole. Acute paraquat poisoning may induce the activities of CYP2C19, and inhibit of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats. This may give advising for reasonable drug use after acute paraquat poisoning.

Keywords: CYP450; UPLC-MS/MS; cocktail; paraquat; rat.

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Figures

Figure 1
Figure 1
The pharmacokinetics profiles of bupropion, omeprazole, phenacetin, tolbutamide, midazolam and Metoprolol in control-group and paraquat-group rats (n = 10).
See this image and copyright information in PMC

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