Clotrimazole protects the liver against normothermic ischemia-reperfusion injury in rats.
作者： A. Iannelli , G. de Sousa , N. Zucchini , L. Peyre , J. Gugenheim
DOI: 10.1016/J.TRANSPROCEED.2009.08.074
关键词: Adenosine 、 Heat shock protein 、 Alanine transaminase 、 Pregnane X receptor 、 Pathology 、 Medicine 、 Endocrinology 、 Transplantation 、 Reperfusion injury 、 Internal medicine 、 Transactivation 、 CYP3A
摘要: Abstract Objective To investigate the possible antiapoptotic prosurvival role of pregnane X receptor (PXR) in hepatic ischemia-reperfusion injury rats using clotrimazole (CTZ), a strong PXR transactivator. Materials and Methods Male Sprague-Dawley were divided into 3 groups 6 each: sham-treated, control, CTZ-treated animals. Control animals subjected to 30 minutes normothermic ischemia whole liver followed by hours reperfusion. The then killed, was excised blood samples collected. Results Clotrimazole induced significant increase expression CYP3A gene, indicating transactivation, whereas Bcl-xL gene not increased. Serum concentrations aspartate aminotransaminase alanine lower than control (difference significant). Levels poly(adenosine diphosphate–ribose) polymerase, caspase-3 substrate, remained significantly higher group compared with controls ( P heat shock proteins 27, 70 90 Conclusion Clotrimazole-mediated transactivation protects against apoptosis rats. Phospho-p 44/42 extracellular signal-regulated kinase 1,2 is activated, 70, downregulated induction PXR.
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sci-hub.se 参考文章(12)
RAFFAELE CURSIO, JEAN GUGENHEIM, JEAN EHRLAND RICCI, DOMINIQUE CRENESSE, PHILIPPE ROSTAGNO, LAURENCE MAULON, MARIE-CHRISTINE SAINT-PAUL, BERNARD FERRUA, PATRICK AUBERGER, A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis The FASEB Journal. ,vol. 13, pp. 253- 261 ,(1999) , 10.1096/FASEBJ.13.2.253
D S Latchman, Katz, J Galea-Lauri, A J Richardson, Increased Heat Shock Protein 90 (hsp90) Expression Leads to Increased Apoptosis in the Monoblastoid Cell Line U937 Following Induction With TNF-alpha and Cycloheximide: A Possible Role in Immunopathology Journal of Immunology. ,vol. 157, pp. 4109- 4118 ,(1996)
Y. A. Lazebnik, S. H. Kaufmann, S. Desnoyers, G. G. Poirier, W. C. Earnshaw, Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE Nature. ,vol. 371, pp. 346- 347 ,(1994) , 10.1038/371346A0
Nathalie Zucchini, Georges de Sousa, Béatrice Bailly-Maitre, Jean Gugenheim, Rémi Bars, Géraldine Lemaire, Roger Rahmani, Regulation of Bcl-2 and Bcl-xL anti-apoptotic protein expression by nuclear receptor PXR in primary cultures of human and rat hepatocytes. Biochimica et Biophysica Acta. ,vol. 1745, pp. 48- 58 ,(2005) , 10.1016/J.BBAMCR.2005.02.005
G. Bertilsson, J. Heidrich, K. Svensson, M. Asman, L. Jendeberg, M. Sydow-Backman, R. Ohlsson, H. Postlind, P. Blomquist, A. Berkenstam, Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction Proceedings of the National Academy of Sciences of the United States of America. ,vol. 95, pp. 12208- 12213 ,(1998) , 10.1073/PNAS.95.21.12208
B Bailly-Maitre, G de Sousa, K Boulukos, J Gugenheim, R Rahmani, Dexamethasone inhibits spontaneous apoptosis in primary cultures of human and rat hepatocytes via Bcl-2 and Bcl-xL induction Cell Death & Differentiation. ,vol. 8, pp. 279- 288 ,(2001) , 10.1038/SJ.CDD.4400815
Douglas G. Farmer, Farin Amersi, Jerzy Kupiec-Weglinski, Ronald W. Busuttil, Current status of ischemia and reperfusion injury in the liver Transplantation Reviews. ,vol. 14, pp. 106- 126 ,(2000) , 10.1053/TR.2000.4651
H. M. Beere, Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways Journal of Clinical Investigation. ,vol. 115, pp. 2633- 2639 ,(2005) , 10.1172/JCI26471
Piotr Chomczynski, Nicoletta Sacchi, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Analytical Biochemistry. ,vol. 162, pp. 156- 159 ,(1987) , 10.1016/0003-2697(87)90021-2
Satoru Kakizaki, Yuichi Yamazaki, Daichi Takizawa, Masahiko Negishi, New insights on the xenobiotic-sensing nuclear receptors in liver diseases--CAR and PXR--. Current Drug Metabolism. ,vol. 9, pp. 614- 621 ,(2008) , 10.2174/138920008785821666