Author(s)

Hailin Wang¹, Lianqiang Hui¹, Chun Li¹, Ting Liu^1*, Chang’an Yu², Chunyu Cao¹, Ran Hao¹, Yi Zhang¹

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
²China-Japanese Friendship Hospital, Beijing, China.

Precision-cut liver slice has been successfully used to study the mechanism of drug-induced hepatotoxicity, the prediction of liver toxicity, the discovery of early hepatic toxicity biomarker and the metabolism of drug in liver. We detected the expression of CYP3A4, CYP2B1 + CYP2B2 and CYP2E1 in precision-cut liver slice after co-cultured with monocrotaline or Tussilago farfara alkaloids to investigate the hepatotoxicity mechanism of those drugs. After co-culturing with monocrotaline or Tussilago farfara alkaloids for 6 hours, the expression of CYP3A4 in the microsome of precision-cut liver slices was detected by Western blot, and the expressions of CYP2B1 + CYP2B2 and CYP2E1 were detected by immunofluorescence. The results showed that monocrotaline induced the expression of CYP3A4 and CYP2B1 + CYP2B2, and Tussilago farfara alkaloids obviously up-regulated the expression of CYP2E1 and CYP3A4. Thus, we conclude that the up-regulation of CYP3A4, CYP2B1 + CYP2B2 and CYP2E1 may be one of the toxic mechanisms of liver injury of those drugs.

Precision-Cut Liver Slices, Monocrotaline, Tussilago farfara Alkaloids, Hepatotoxity, Cytochrome P450 Enzymes

Wang, H. , Hui, L. , Li, C. , Liu, T. , Yu, C. , Cao, C. , Hao, R. and Zhang, Y. (2016) Application of Precision-Cut Rat Liver Slice to Study the Influence of Monocrotaline, Tussilago farfara Alkaloids on the Expression of Cytochrome P450 Enzymes. Health, 8, 370-379. doi: 10.4236/health.2016.84039.