TITLE:
Application of Precision-Cut Rat Liver Slice to Study the Influence of Monocrotaline, Tussilago farfara Alkaloids on the Expression of Cytochrome P450 Enzymes
AUTHORS:
Hailin Wang, Lianqiang Hui, Chun Li, Ting Liu, Chang’an Yu, Chunyu Cao, Ran Hao, Yi Zhang
KEYWORDS:
Precision-Cut Liver Slices, Monocrotaline, Tussilago farfara Alkaloids, Hepatotoxity, Cytochrome P450 Enzymes
JOURNAL NAME:
Health,
Vol.8 No.4,
February
29,
2016
ABSTRACT: 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.