Enantioselective metabolism and toxic effects of metalaxyl on primary hepatocytes from rat.
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.
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
X
Wang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Yuanmingyuan west road 2, Beijing, 100193, China.
Wentao
W
Zhu
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
J
Qiu
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Yuanmingyuan west road 2, Beijing, 100193, China.
Ping
P
Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Yuanmingyuan west road 2, Beijing, 100193, China.
Yao
Y
Wang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Yuanmingyuan west road 2, Beijing, 100193, China. zqzhou@cau.edu.cn.
Zhiqiang
Z
Zhou
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D005659:Fungicides, Industrial / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D005659:Fungicides, Industrial; C028175:metalaxyl; D000409:Alanine
Cytotoxicity; Hepatocyte; Metabolite; Metalaxyl enantiomers; Oxidative damage; Stereoselective metabolism