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.
Highlights
Precision-cut liver slice is an advanced technology between organ and cell levels, integrating in vivo and in vitro detecting techniques, which is simple, rapid, economic and can be used to predict drug toxicity [1]-[5]
Based on the previous results, this research further tests the expression of CYP3A4, CYP2B and CYP2E1 after monocrotaline or Tussilago farfara alkaloids co-cultured with precision-cut liver slices for 6 hours to observe regulatory effect of those traditional Chinese medicine (TCM) contained Pyrrolizidine alkaloids (PAs) on cytochrome P450s (CYP450s)
The Effect of Monocrotaline, Tussilago farfara Alkaloids on the Expression of CYP3A4 There was no significant difference in mean optical density value between the control group and 0.5% DMSO group
Summary
Precision-cut liver slice is an advanced technology between organ and cell levels, integrating in vivo and in vitro detecting techniques, which is simple, rapid, economic and can be used to predict drug toxicity [1]-[5]. Precision-cut liver slice has been successfully used in the study of drug toxicity mechanism and prediction, the discovery of early toxicity markers and drug metabolism and transformation. Our past research has found that co-culture of monocrotaline and precision-cut liver slices for 24 hours can damage the liver cell membrane to a certain degree, cause LDH leakage increased and protein content decreased, and those changes become aggravated with the increase of monocrotaline dose [23]. Based on the previous results, this research further tests the expression of CYP3A4, CYP2B and CYP2E1 after monocrotaline or Tussilago farfara alkaloids co-cultured with precision-cut liver slices for 6 hours to observe regulatory effect of those TCM contained PAs on CYP450s
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