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

International Journal of Environmental Research and Public Health

Guolin Shen¹  Cheng Wang¹  Lili Zhou²  Lei Li²  Huiming Chen²  Wenlian Yu¹  Haishan Li¹ 

[1] Chinese Academy of Inspection and Quarantine, Beijing 100123, China;

关键词: thiacalix[4]arene tetrasulfonate;    CYP450;    hepatocyte;    metabolism;   

DOI  :  10.3390/ijerph120910783

来源: mdpi

【 摘 要 】

In this study, we investigated the enzymes catalyzing the phaseⅠmetabolism 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. IC₅₀ 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.