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Stereoselective Toxicity and Metabolism of Lactofen in Primary Hepatocytes From Rat
Author(s) -
Wang Xinru,
Diao Jinling,
Shen Zhigang,
Zhu Wentao,
Zhang Ping,
Zhou Zhiqiang
Publication year - 2013
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22207
Subject(s) - chemistry , toxicity , metabolism , primary (astronomy) , stereoselectivity , biochemistry , environmental chemistry , organic chemistry , physics , astronomy , catalysis
The stereoselective metabolism of lactofen in primary rat hepatocytes was studied using a chiral high‐performance liquid chromatographic (HPLC) method. Rac ‐lactofen and its two enantiomers, S‐(+)‐ and R‐(−)‐lactofen, as well as two of its major metabolites, acifluorfen, S‐(+)‐ and R‐(−)‐desethyl lactofen, were used as substrates,. The single and joint cytotoxicity of parent compounds and the metabolites were assessed by coincubation with rat hepatocytes as target cells. Cytotoxicity was determined by the methyl tetrazolium (MTT) assay. In hepatocyte incubations, S‐(+)‐lactofen was degraded more rapidly than R‐(−)‐lactofen, and a stereospecific formation of S‐(+)‐desethyl lactofen was detected. Metabolism of lactofen to desethyl lactofen was processed with the retention of configuration, and the achiral compound, acifluorfen, was the shared metabolite generated from both S‐(+)‐ and R‐(−)‐lactofen. There was no chiral conversion of lactofen or desethyl lactofen enantiomers during the incubation. For the cytotoxicity research, the calculated EC 50 values indicated that when being applied individually, the parent compound was less toxic than its metabolites, while the combination with metabolites enhanced its cytotoxic effects. The data presented here would be helpful for a more comprehensive assessment of the ecotoxicological and environmental risks of lactofen. Chirality 25:743–750, 2013 . © 2013 Wiley Periodicals, Inc.