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  • Title: Gender-related in vitro metabolism of hexaconazole and its enantiomers in rats.
    Author: Shen Z, Liu D, Wang P, Zhang P, Wang X, Zhou Z.
    Journal: Chirality; 2013 Dec; 25(12):852-7. PubMed ID: 24027055.
    Abstract:
    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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