Stereoselective metabolism of benalaxyl in liver microsomes from rat and rabbit

Zhang, Ping; Zhu, Wentao; Dang, Ziheng; Shen, Zhigang; Xu, Xinyuan; Huang, Ledan; Zhou, Zhiqiang

doi:10.1002/chir.20879

Cited by 14 publications

(13 citation statements)

References 21 publications

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“…The metabolism of benalaxyl in rats and rabbits liver microsomes was similar to ethofumesate. In rat liver, microsomes (+)‐ S ‐ benalaxyl was degraded faster than its antipode; on the contrary, (−)‐ R ‐ benalaxyl was degraded faster than (+)‐ S ‐ benalaxyl in rabbit liver microsomes . The P450 family of enzymes can be inhibited, activated, or induced by concomitant xenobiotic treatment, so the xenobiotic–xenobiotic interactions may alter the enantioselective behavior of enantiomers.…”

Section: Resultsmentioning

confidence: 99%

“…In rat liver, microsomes (+)-S-benalaxyl was degraded faster than its antipode; on the contrary, (À)-R-benalaxyl was degraded faster than (+)-S-benalaxyl in rabbit liver microsomes. 25 The P450 family of enzymes can be inhibited, activated, or induced by concomitant xenobiotic treatment, so the xenobiotic-xenobiotic interactions may alter the enantioselective behavior of enantiomers. These important areas are not considered in detail in this concept paper.…”

Section: Gender-related Differences In Metabolism Of Hexaconazolementioning

confidence: 99%

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Gender‐Related In Vitro Metabolism of Hexaconazole and Its Enantiomers in Rats

et al. 2013

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In the present study we investigated the enantioselective disappearance of hexaconazole in rat liver microsomes system prepared from both genders. High-performance liquid chromatography (HPLC) was used for identification and quantification. The degradation of the (+)-hexaconazole was faster than that of the (-)-hexaconazole in racemic hexaconazole and single enantiomer incubation in both sexes. The degradation half-life of the (+)-hexaconazole or (-)-hexaconazole was also gender-related. The metabolism of (+)-hexaconazole and (-)-hexaconazole were faster in male rat hepatic microsomes than that in female, suggesting that at least one of the cytochrome P450s (CYP) in the male rat liver microsomes system responsible for hexaconazole metabolism was male-specific or considerably more active. Kinetic assays showed that the intrinsic clearance in male rat liver microsomes was higher than that in female. All these results strongly suggest that sexual dimorphic metabolism of hexaconazole exists in rats. The inhibition experiments with CYP inhibitors showed that the inhibitory effect of inhibitors was enantioselective and affected by sex. The results suggest that the enantioselective metabolism of hexaconazole was determined by the amount of hepatic cytochrome P450 and the expression of individual isoforms of CYPs.

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Section: Resultsmentioning

confidence: 99%

Section: Gender-related Differences In Metabolism Of Hexaconazolementioning

confidence: 99%

Gender‐Related In Vitro Metabolism of Hexaconazole and Its Enantiomers in Rats

et al. 2013

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“…The procedure of preparation of rabbit hepatic microsomes from rabbits (Japanese white rabbit, male, Approximately 2 kg, provided by the Experimental Animal Research Institute of China Agriculture University) followed the method of Zhang et al12 and the microsomes were immediately stored at −80°C. Hepatic microsomal activity was determined according to the method of Bradford with BSA as the standard.…”

Section: Methodsmentioning

confidence: 99%

Stereoselective metabolism of fenoxaprop‐ethyl and its chiral metabolite fenoxaprop in rabbits

Zhang

Shen

et al. 2011

Chirality

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The stereoselective metabolism of the enantiomers of fenoxaprop-ethyl (FE) and its primary chiral metabolite fenoxaprop (FA) in rabbits in vivo and in vitro was studied based on a validated chiral high-performance liquid chromatography method. The information of in vivo metabolism was obtained by intravenous administration of racemic FE, racemic FA, and optically pure (-)-(S)-FE and (+)-(R)-FE separately. The results showed that FE degraded very fast to the metabolite FA, which was then metabolized in a stereoselective way in vivo: (-)-(S)-FA degraded faster in plasma, heart, lung, liver, kidney, and bile than its antipode. Moreover, a conversion of (-)-(S)-FA to (+)-(R)-FA in plasma was found after injection of optically pure (-)-(S)- and (+)-(R)-FE separately. Either enantiomers were not detected in brain, spleen, muscle, and fat. Plasma concentration-time curves were best described by an open three-compartment model, and the toxicokinetic parameters of the two enantiomers were significantly different. Different metabolism behaviors were observed in the degradations of FE and FA in the plasma and liver microsomes in vitro, which were helpful for understanding the stereoselective mechanism. This work suggested the stereoselective behaviors of chiral pollutants, and their chiral metabolites in environment should be taken into account for an accurate risk assessment.

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“…In the study of environmental behavior, the researchers reported differences in dissipation rate of the two enantiomers in plants such as tomato, tobacco, sugar beet, capsicum, cucumber, and Scenedesmus obliquus . Meanwhile, the stereoselective degradation of benalaxyl was also found in animals such as earthworm, rat, and rabbit . More important, the enantioselective toxicity of benalaxyl was investigated by researchers.…”

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confidence: 99%

“…17,22 Meanwhile, the stereoselective degradation of benalaxyl was also found in animals such as earthworm, rat, and rabbit. 20,23,24 More important, the enantioselective toxicity of benalaxyl was investigated by researchers. It was found that the two enantiomers of benalaxyl exhibited different acute toxicity to earthworm (Eisenia fedtia) and freshwater algae (Scenedesmus obliquus), and R-(À)benalaxyl showed much higher toxicity to both organisms.…”

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confidence: 99%

Stereoselective Behavior of the Fungicide Benalaxyl During Grape Growth and the Wine‐Making Process

Yihua

Dai

et al. 2016

Chirality

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Benalaxyl is widely applied as a fungicide during grape planting processing. In this experiment, the stereoselective behavior of benalaxyl was studied during the grape growth and wine-making process. A simple method based on high-performance liquid chromatography (HPLC) equipped with a chiral column and UV detector was established to separate and determine the enantiomers of benalaxyl. Stereoselective degradation of the two enantiomers of benalaxyl was found in grapes. The degradation of both enantiomers followed pseudofirst-order kinetics, and the degradation rate of R-(-)-benalaxyl was faster than S-(+)-benalaxyl. The half-life of R-(-)-benalaxyl was 27 h, while the half-life of S-(+)-benalaxyl was 31 h. The enantiomer fraction value decreased from 0.50 to 0.34 and finally only S-(+)-benalaxyl could be detected. In the fermentation process, both enantiomers of benalaxyl were hardly degraded, and no configuration interconversion was observed. Meanwhile, both enantiomers of benalaxyl showed little influence on the growth of the yeast, consumption of carbon sources, or production of alcohol. The result of this study might provide more sufficient data for the evaluation of food safety and potential risk. Chirality 28:394-398, 2016. © 2016 Wiley Periodicals, Inc.

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Stereoselective metabolism of benalaxyl in liver microsomes from rat and rabbit

Cited by 14 publications

References 21 publications

Gender‐Related In Vitro Metabolism of Hexaconazole and Its Enantiomers in Rats

Gender‐Related In Vitro Metabolism of Hexaconazole and Its Enantiomers in Rats

Stereoselective metabolism of fenoxaprop‐ethyl and its chiral metabolite fenoxaprop in rabbits

Stereoselective Behavior of the Fungicide Benalaxyl During Grape Growth and the Wine‐Making Process

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