Environmental Science and Pollution Research

, Volume 23, Issue 18, pp 18649–18656 | Cite as

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

  • Xinru Wang
  • Wentao Zhu
  • Jing Qiu
  • Ping Zhang
  • Yao Wang
  • Zhiqiang ZhouEmail author
Research Article


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.


Oxidative damage Cytotoxicity Hepatocyte Stereoselective metabolism Metalaxyl enantiomers Metabolite 



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

Compliance with ethical standards

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

Supplementary material

11356_2016_6797_MOESM1_ESM.docx (97 kb)
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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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Xinru Wang
    • 1
  • Wentao Zhu
    • 1
  • Jing Qiu
    • 2
  • Ping Zhang
    • 1
  • Yao Wang
    • 1
  • Zhiqiang Zhou
    • 1
    Email author
  1. 1.Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied ChemistryChina Agricultural UniversityBeijingChina
  2. 2.Institute of Quality Standards and Testing Technology for Agro-Products, Key Laboratory of Agro-product Quality and SafetyBeijingChinese Academy of Agricultural SciencesBeijingChina

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