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 — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
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
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
,
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
,
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
,
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
,
China-Japanese Friendship Hospital, Beijing, China
,
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
,
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
,
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
1 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
2 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
3 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
4 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
5 China-Japanese Friendship Hospital, Beijing, China
6 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
7 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
8 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 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.
Catania, J.R., McGarrigle, B.P., Rittenhouse-Olson, K. and Olson, J.R. (2007) Induction of CYP2B and CYP2E1 in Precision-Cut Rat Liver Slices Cultured in Defined Medium. Toxicology in Vitro, 21, 109-115. http://dx.doi.org/10.1016/j.tiv.2006.08.001
Neyrinck, A.M., Gomez, C. and Delzenne, N.M. (2004) Precision-Cut Liver Slices in Culture as a Tool to Assess the Physiological Involvement of Kupffer Cells in Hepatic Metabolism. Comparative Hepatology, 3, S45. http://dx.doi.org/10.1186/1476-5926-2-S1-S45
Lake, B.G., Charzat, C., Tredger, J.M, . Renwick, A.B., Beamand, J.A. and Price, R.J. (1996) Induction of Cytochrome P450 Isoenzymes in Cultured Precision-Cut Rat and Human Liver Slices. Xenobiotica, 26, 297-306. http://dx.doi.org/10.3109/00498259609046709
Lerche-Langrand, C. and Toutain, H.J. (2000) Precision-Cut Liver Slices: Characteristics and Use for in Vitro Pharmaco-Toxicology. Toxicology, 153, 221-253. http://dx.doi.org/10.3109/00498259609046709
Lupp, A., Danz, M. and Müller, D. (2001) Morphology and Cytochrome P450 Isoforms Expression in Precision-Cut Rat Liver Slices. Toxicology, 161, 53-66. http://dx.doi.org/10.1016/S0300-483X(01)00333-X
Krumdieck, C.L., dos Santos, J.E. and Ho, K.J. (1980) A New Instrument for the Rapid Preparation of Tissue Slices. Analytical Biochemistry, 104, 118-123. http://dx.doi.org/10.1016/0003-2697(80)90284-5
Behrsing, H.P., Vickers, A.E. and Tyson, C.A. (2003) Extended Rat Liver Slice Survival and Stability Monitored Using Clinical Biomarkers. Biochemical and Biophysical Research Communications, 312, 209-213. http://dx.doi.org/10.1016/0003-2697(80)90284-5
van Midwoud, P.M., Groothuis, G.M., Merema, M.T. and Verpoorte, E. (2010) Microfluidic Biochip for the Perifusion of Precision-Cut Rat Liver Slices for Metabolism and Toxicology Studies. Biotechnology and Bioengineering, 105, 184-194. http://dx.doi.org/10.1002/bit.22516
de Graaf, I.A., Olinga, P., de Jager, M.H., Merema, M.T., de Kanter, R., van de Kerkhof, E.G. and Groothuis, G.M. (2010) Preparation and Incubation of Precision-Cut Liver and Intestinal Slices for Application in Drug Metabolism and Toxicity Studies. Nature Protocols, 5, 1540-1551. http://dx.doi.org/10.1002/bit.22516
Geng, X.C., Shen, L.Z., Li, B. and Wang, J.Z. (2011) Progress of Biomarkers for Hepatic Toxicity. Chinese Pharmaceutical Journal, 46, 721-725.
Wang, J., Wang, C.H. and Wang, Z.T. (2007) Advancement of Investigation on Cytotoxicity and Mechanism of Pyrrolizidine Alkaloids. International Journal of Pharmaceutical Research, 34, 246-249, 258.
Liu, P. (2004) Liver Injuries Caused by Chinese Herbs. Chinese Journal of Hepatology, 12, 243.
Zeng, M.Y., Li, M.M. and Zhao, X.W. (1996) Traditional Chinese Medicine Containing Pyrrolizidine Alkaloids and Its Toxicity(2)-Tussilago farfara L. and Petasites japonicas miq.etc. Traditional Chinese Drug Research and Clinical Pharmacology, 7, 51-52.
Keller, K., Hansel, R., De Smet, P.A.G.M. and Chandler, R.F. (1992) Adverse Effects of Herbal Drugs. Vol. 1, Springer-Verlag, Berlin Heidelberg, 191-206, 211-214.
Williams, G.M., Mori, H., Hirono, I. and Nagao, M. (1980) Genotoxicity of Pyrrolizidine Alkaloids in the Hepatocyte Primary Culture/DNA-Repair Test. Mutation Research/Genetic Toxicology, 79, 1-5. http://dx.doi.org/10.1016/0165-1218(80)90141-X
Müller, L., Kasper, P. and Kaufmann, G. (1992) The Clastogenic Potential in Vitro of Pyrrolizidine Alkaloids Employing Hepatocyte Metabolism. Mutation Research/Genetic Toxicology, 282, 169-176. http://dx.doi.org/10.1016/0165-7992(92)90091-U
Wagner, J.G., Petry, T.W. and Roth, R.A. (1993) Characterization of Monocrotalinepyrrole-Induced DNA Cross-Linking in Pulmonary Artery Endothelium. American Journal of Physiology, 264, L517-L522.
Zhang, G.S. (2003) Cytochrome P450 and Drug Induced Liver Injury. Journal of Jinzhou Medical College, 5, 45-47.
Kaplowitz, N. (2002) Biochemical and Cellular Mechanisms of Toxic Liver Injury. Seminars in Liver Disease, 22, 137-144. http://dx.doi.org/10.1055/s-2002-30100
Vuilleumier, N., Rossier, M.F. and Chiappe, A. (2006) CYP2E1 Genotype Andi-Soniazid-Induced Hepatotoxicity in Patients Treated for Latent Tuber-Culosis. European Journal of Clinical Pharmacology, 62, 423-429. http://dx.doi.org/10.1007/s00228-006-0111-5
Wolf, K.K., Wood, S.G., Allard, J.L., Hunt, J.A., Gorman, N., Walton-Strong, B.W., et al. (2007) Role of CYP3A and CYP2E1 in Alcohol-Mediated Increases in Acetaminophen Hepato-Toxicity: Comparison of Wild-Type and Cyp2e1(-/-) Mice. Drug Metabolism and Disposition, 35, 1223-1231. http://dx.doi.org/10.1124/dmd.107.014738
Yao, J.-C., Rao, J., Zeng, L.-G., Zhang, L.-Y., Jiang, Z.-Z., He, L., Hu, L. and Zhao, X.-Y. (2010) Metabolism and Enzyme Kinetics of Triptolide in Rat Liver Microsomes. China Pharmacy, 7, 577-580.
Hui, L.Q., Gao, S.R., Liu, T., Cao, C.Y., Guo, J., Hao, R., Yi, Y., Li, C.Y., Zhao, Y. and Liang, A.H. (2011) Evaluation of Vitro Hepatotoxicity of Monocrotaline by Precision-Cut Liver Slice Technique. China Journal of Chinese Materia Medica, 36, 628-632.
Hui, L.Q., Gao, S.R., Liu, T., Li, C.Y., Hao, R., Yi, Y., Guo, J., He, R., Cao, C.Y., Zhao, Y., Liang, A.H. and Zhang, Y. (2012) Hepatotoxicity on Water Extracts and the Total Alkaloid of Farfarae Flos. Chinese Journal of Experimental Traditional Medical Formulae, 18, 238-241.
Pu, S.B., Xu, D.R., Zhang, M., Zhou, H.H., Wang, Z.T. and Yu, G.D. (2004) The Detection of Hepatotoxic Pyrrolizidine Alkaloids in Flos Farfarae by LC/MSn. Chinese Journal of Natural Medicines, 2, 293-297.
Pessayre, D. (1995) Role of Reactive Metabolites in Drug-Induced Hepatitis. Journal of Hepatology, 23, 16-24.
Ma, K.F., Xie, X.J., Liu, Y. and Jia, H.Y. (2013) Progress in Genetic Polymorphism of Cytochrome P450 Enzymes and Drug-Induced Liver Injury. Chinese Journal of Pharmacology and Toxicology, 27, 889-892.
Bozina, N., Bradamante, V. and Lovric, M. (2009) Genetic Polymorghism of Metabolic Enzymes P450(CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk. Archives of Industrial Hygiene and Toxicology, 60, 217-242. http://dx.doi.org/10.2478/10004-1254-60-2009-1885
Yan, M.F., Hao, F.R., Xu, L.M., Tong, S.G., Ji, H.J., Shen, Z.F. and Jin, Y.Z. (2005) Effects of Mitomycin(MMC) and γ-Ray Irradiation on Cytochome p450 Content and Activities of CYP2B1 and CYP2E1 in Rats. Journal of Radiation Research and Radiation Processing, 23, 246-250.
Graaf, I.A., Groothuis, G.M. and Olinga, P. (2007) Precision-Cut Tissue Slices as a Tool to Predict Metabolism of Novel Drugs. Expert Opinion on Drug Metabolism & Toxicology, 3, 879-898. http://dx.doi.org/10.1517/17425255.3.6.879
Olinga, P., Groen, K., Hof, I.H., De Kanter, R., Koster, H.J., Leeman, W.R., Rutten, A.A., Van Twillert, K. and Groothuis, G.M. (1997) Comparison of Five Incubation Systems for Rat Liver Slices Using Functional and Viability Parameters. Journal of Pharmacological and Toxicological Methods, 38, 59-69. http://dx.doi.org/10.1016/s1056-8719(97)00060-9
Vanden Branden, M., Wrighton, S.A., Ekins, S., Gillespie, J.S., Binkley, S.N., Ring, B.J., Gadberry, M.G., Mullins, D.C., Strom, S.C. and Jensen, C.B. (1998) Alterations of the Catalytic Activities of Drug-Metabolizing Enzymes in Cultures of Human Liver Slices. Drug Metabolism and Disposition, 26, 1063-1068.
Xu, L.M. (2005) Understanding and Prevention of Liver Damage Caused by Chinese Herbal Medicine. Journal of Modern Medicine & Health, 21, 379-380.