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Enantioselective metabolism and toxic effects of metalaxyl on primary hepatocytes from rat

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Abstract

Enantiomers of chiral compounds often exhibit enantioselective adverse effects and biochemical processes in non-target organisms. In this study, enantioselective metabolism and toxic effects of metalaxyl enantiomers on primary rat hepatocytes were investigated. Stereoselectivity was observed on both degradation of metalaxyl and formation of metabolites. (−)-R-metalaxyl eliminated faster than (+)-S-metalaxyl, while the hydroxylmetalaxyl, demethylmetalaxyl, and didemethylmetalaxyl metabolites derived from 50-μM (+)-S-metalaxyl after 24 h of incubation were approximately 1.57, 1.43, and 1.86 times more than that of (−)-R-metalaxyl, respectively. According to the methyl tetrazolium (MTT) assay, the EC50 values (24 h) for rac-, (+)-S-, and (−)-R-metalaxyl were 1788.22, 2066.73, and 2263.71 μM, respectively. An accordant enantioselective effect on oxidative stress suggested that the enantioselective cytotoxicity induced by metalaxyl enantiomers may partly contribute to enantioselective oxidative damage and mitochondrial dysfunction. Such results could be of great importance for credible environmental and toxicological risk assessment of metalaxyl.

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Acknowledgements

We gratefully acknowledge financial support from the National Natural Science Foundation of China (21207158, 21337005) and Chinese Universities Scientific Fund (2012RC026).

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    Authors and Affiliations

    1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Yuanmingyuan west road 2, Beijing, 100193, China

      Xinru Wang, Wentao Zhu, Ping Zhang, Yao Wang & Zhiqiang Zhou

    2. Institute of Quality Standards and Testing Technology for Agro-Products, Key Laboratory of Agro-product Quality and SafetyBeijing, Chinese Academy of Agricultural Sciences, Beijing, China

      Jing Qiu

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    1. Xinru Wang
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    2. Wentao Zhu
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    3. Jing Qiu
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    5. Yao Wang
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    Correspondence to Zhiqiang Zhou.

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    All animal experiments were performed in accordance with the current Chinese legislation and approved by the independent animal ethical committee at China Agricultural University.

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    Responsible editor: Philippe Garrigues

    Xinru Wang and Wentao Zhu contributed equally to this work.

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    Figure S1

    Cytotoxicity results of (A)rac-metalaxyl, (B) (+)-S-metalaxyl,(C) (-)-R-metalaxyl after 12h exposure and (D)rac-metalaxyl, (E) (+)-S-metalaxyl,(F) (-)-R-metalaxyl after 24h exposure (DOCX 97 kb)

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    Wang, X., Zhu, W., Qiu, J. et al. Enantioselective metabolism and toxic effects of metalaxyl on primary hepatocytes from rat. Environ Sci Pollut Res 23, 18649–18656 (2016). https://doi.org/10.1007/s11356-016-6797-8

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    • DOI: https://doi.org/10.1007/s11356-016-6797-8

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