Application of Precision-Cut Rat Liver Slice to Study the Influence of Monocrotaline, <i>Tussilago farfara</i> Alkaloids on the Expression of Cytochrome P450 Enzymes

Precision-cut liverslice has been successfully used to study the mechanism of drug-induced hepatotoxicity,the prediction of liver toxicity, the discovery of early hepatic toxicity biomarkerand the metabolism of drug in liver. We detected the expression of CYP3A4, CYP2B1+ CYP2B2 and CYP2E1 in precision-cut liver slice after co-cultured withmonocrotaline or Tussilago farfara alkaloids to investigate the hepatotoxicity mechanism of those drugs. Afterco-culturing with monocrotaline or Tussilagofarfara alkaloids for 6 hours, the expression of CYP3A4 in the microsome ofprecision-cut liver slices was detected by Western blot, and the expressionsof CYP2B1 + CYP2B2 and CYP2E1 were detected by immunofluorescence. The resultsshowed that monocrotaline induced theexpression of CYP3A4 and CYP2B1 + CYP2B2, and Tussilago farfara alkaloids obviously up-regulated the expression of CYP2E1and 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 thosedrugs.