CYP450 Enzyme-Mediated Metabolism of TCAS and Its Inhibitory and Induced Effects on Metabolized Enzymes in Vitro

Guolin Shen, Cheng Wang, Lili Zhou, Lei Li, Huiming Chen, Wenlian Yu and Haishan Li
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Guolin Shen: Chinese Academy of Inspection and Quarantine, Beijing 100123, China
Cheng Wang: Chinese Academy of Inspection and Quarantine, Beijing 100123, China
Lili Zhou: Chinese Academy of Inspection and Quarantine, Beijing 100123, China
Lei Li: Chinese Academy of Inspection and Quarantine, Beijing 100123, China
Huiming Chen: Chinese Academy of Inspection and Quarantine, Beijing 100123, China
Wenlian Yu: Chinese Academy of Inspection and Quarantine, Beijing 100123, China
Haishan Li: Chinese Academy of Inspection and Quarantine, Beijing 100123, China

IJERPH, 2015, vol. 12, issue 9, 1-11

Abstract: In this study, we investigated the enzymes catalyzing the phase?metabolism of thiacalixarene (TCAS) based on in vitro system including cDNA-expressed P450 enzymes, human liver microsomes plus inhibitors and monoclonal antibodies. In addition, the inhibitory potential of TCAS on major CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2B6, CYP2D6 and CYP3A4) was assessed. The results showed that CYP1A2 and CYP2C9 mediated TCAS hydroxylation. IC 50 values for TCAS in rat and human liver microsomes were greater than 50 µM, and it demonstrated a weak inhibition of rat and human CYP450 enzymes. Finally, sandwiched hepatocytes were used to evaluate the induction of CYP1A and CYP3A to define the function of TCAS in vivo. The results showed that incubation of TCAS at different concentrations for 72 h failed to induce CYP1A and CYP3A. However, incubation of the cells with 50 and 100 µM TCAS caused a profound decrease in the activities of CYP1A and CYP3A, which was probably due to cytotoxic effects, suggesting that exposure to TCAS might be a health concern.

Keywords: thiacalix[4]arene tetrasulfonate; CYP450; hepatocyte; metabolism (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2015
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