Identifying Metabolic Perturbations and Toxic Effects of Rac-Metalaxyl and Metalaxyl-M in Mice Using Integrative NMR and UPLC-MS/MS Based Metabolomics PMID: 31683916

ADC Targets in Oncology

2026-04-10

Identifying Metabolic Perturbations and Toxic Effects of Rac-Metalaxyl and Metalaxyl-M in Mice Using Integrative NMR and UPLC-MS/MS Based Metabolomics

Int J Mol Sci. 2019 Nov 1;20(21):5457. doi: 10.3390/ijms20215457.

Ping Zhang ¹ ² ³ , Sheng Wang ⁴ ⁵ , Yuhan He ⁶ ⁷ ⁸ , Yangyang Xu ⁹ ¹⁰ , Dongmei Shi ¹¹ ¹² , Furong Yang ¹³ ¹⁴ , Weizhong Yu ¹⁵ ¹⁶ , Wentao Zhu ¹⁷ , Lin He ¹⁸ ¹⁹ ²⁰

Affiliations

1. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
2. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
3. State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing 400715, China. [email protected].
4. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
5. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
6. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
7. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
8. State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing 400715, China. [email protected].
9. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
10. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
11. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
12. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
13. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
14. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
15. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
16. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
17. Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China. [email protected].
18. Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. [email protected].
19. Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. [email protected].
20. State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing 400715, China. [email protected].

Abstract

Although metabolic perturbations are sensitive indicators for low-dose toxic effects, the metabolic mechanisms affected by rac-metalaxyl and metalaxyl-M in mammals from a metabolic profiling perspective remain unclear. In this study, the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M in mice were carefully investigated using integrative nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based metabolomics. Histopathology, NMR-based untargeted urine profile, multivariate pattern recognition, metabolite identification, pathway analysis, UPLC-MS/MS based targeted serum Amino acids, and tryptophan pathway analysis were determined after rac-metalaxyl and metalaxyl-M exposure, individually. Histopathology indicated that metalaxyl-M induced greater hepatocellular inflammatory, necrosis, and vacuolation in mice than rac-metalaxyl at the same exposure dosage. The metabolic perturbations induced by rac-metalaxyl and metalaxyl-M were directly separated using partial least-squares discriminant analysis (PLS-DA). Furthermore, metabolite identification and pathway analysis indicated that rac-metalaxyl mainly induced ten urine metabolite changes and four pathway fluctuations. However, metalaxyl-M induced 19 urine metabolite changes and six pathway fluctuations. Serum Amino acids and tryptophan pathway metabolite changes induced by rac-metalaxyl and metalaxyl-M were also different even at the same exposure level. Such results may provide specific insight into the metabolic perturbations and toxic effects of rac-metalaxyl and metalaxyl-M, and contribute to providing available data for health risk assessments of rac-metalaxyl and metalaxyl-M at a metabolomics level.

Keywords

NMR; UPLC-MS/MS; amino acids; metabolic perturbation; metabolomics; metalaxyl; tryptophan metabolism.