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Differences in Biological Activities between Recombinant Human Paraoxonase 1 (rhPON1) Subtype Isozemys R/Q as Antidotes against Organophosphrus Poisoning
Toxicology Letters ( IF 3.5 ) Pub Date : 2020-06-01 , DOI: 10.1016/j.toxlet.2020.01.017
Yue Cui 1 , Min Zhao 1 , Lang Han 2
Affiliation  

Paraoxonase 1 (PON1) is a type of aromatic esterase widely existing in mammals. It can hydrolyze various kinds of compounds effectively in vivo and in vitro. Previous studies have confirmed that PON1 can be used as an antidote against organophosphorus poisoning. In this study, we obtained two subtype isozymes of recombinant human PON1 (rhPON1), which have gene polymorphisms in 192 locis, by gene recombination. We then investigated the differences between these two recombinant isozymes (i.e. rhPON1R192 and rhPON1Q192) in their detoxification effect against organophosphorus pesticide poisoning in rats. As antidotes against chlorpyrifos poisoning, the rhPON1R192 isozyme demonstrated better effect than the rhPON1Q192 isozyme; whereas, their detoxification activities against diazinon were on the contrary. Both isozymes showed poor detoxification activity against trithion. Therefore, we concluded that if the PON1 was used as a biological scavenger against organophosphate poisoning, better detoxification effect may be achieved by selecting the PON1 subtype isozyme with higher specific hydrolytic activity.

中文翻译:

重组人对氧磷酶 1 (rhPON1) 亚型 Isozemys R/Q 作为有机磷中毒解毒剂的生物活性差异

对氧磷酶 1 (PON1) 是一种广泛存在于哺乳动物中的芳香族酯酶。它可以在体内和体外有效水解各种化合物。以往的研究证实,PON1可作为有机磷中毒的解毒剂。在本研究中,我们通过基因重组获得了重组人PON1(rhPON1)的两个亚型同工酶,它们在192个位点具有基因多态性。然后我们研究了这两种重组同工酶(即rhPON1R192 和rhPON1Q192)在对大鼠有机磷农药中毒解毒作用方面的差异。作为毒死蜱中毒的解毒剂,rhPON1R192同工酶的作用优于rhPON1Q192同工酶;而它们对二嗪农的解毒作用则相反。两种同工酶对三硫磷的解毒活性都很差。因此,我们得出结论,如果将PON1用作有机磷中毒的生物清除剂,选择具有更高比水解活性的PON1亚型同工酶可以获得更好的解毒效果。
更新日期:2020-06-01
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