Clotrimazole protects the liver against normothermic ischemia-reperfusion injury in rats. 2009

A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
Service de Chirurgie Digestive et Transplantation Hépatique, Hôpital Archet 2, 151 Rte Saint Antoine de Ginestière BP 3079, Nice Cedex 3, France. antonio_iannelli@hotmail.com

OBJECTIVE To investigate the possible antiapoptotic prosurvival role of the pregnane X receptor (PXR) in hepatic ischemia-reperfusion injury in rats using clotrimazole (CTZ), a strong PXR transactivator. METHODS Male Sprague-Dawley rats were divided into 3 groups of 6 each: sham-treated, control, and CTZ-treated animals. Control and CTZ-treated animals were subjected to 30 minutes of normothermic ischemia of the whole liver followed by 6 hours of reperfusion. The animals were then killed, and the liver was excised and blood samples collected. RESULTS Clotrimazole induced a significant increase in expression of the CYP3A gene, indicating PXR transactivation, whereas expression of the antiapoptotic Bcl-xL gene was not increased. Serum concentrations of aspartate aminotransaminase and alanine aminotransaminase were lower in CTZ-treated animals than in control animals (difference not significant). Levels of poly(adenosine diphosphate-ribose) polymerase, a caspase-3 substrate, remained significantly higher in the CTZ-treated group compared with controls (P < .05). Clotrimazole increased the expression of phospho-p 44/42 extracellular signal-regulated kinase 1,2 (P < .05). The gene expression of the heat shock proteins 27, 70 and 90 was significantly lower in CTZ-treated animals than in controls (P < .05). CONCLUSIONS Clotrimazole-mediated PXR transactivation protects the liver against ischemia-reperfusion apoptosis in rats. Phospho-p 44/42 extracellular signal-regulated kinase 1,2 is activated, whereas gene expression of heat shock proteins 27, 70, and 90 is downregulated by induction of PXR.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D003022 Clotrimazole An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal CELL MEMBRANES. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Bay b 5097,Canesten,FB b 5097,Kanesten,Klotrimazole,Lotrimin,Mycelex
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D000410 Alanine Transaminase An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. Alanine Aminotransferase,Glutamic-Pyruvic Transaminase,SGPT,Alanine-2-Oxoglutarate Aminotransferase,Glutamic-Alanine Transaminase,Alanine 2 Oxoglutarate Aminotransferase,Aminotransferase, Alanine,Aminotransferase, Alanine-2-Oxoglutarate,Glutamic Alanine Transaminase,Glutamic Pyruvic Transaminase,Transaminase, Alanine,Transaminase, Glutamic-Alanine,Transaminase, Glutamic-Pyruvic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001219 Aspartate Aminotransferases Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1. Aspartate Aminotransferase,Aspartate Transaminase,Glutamic-Oxaloacetic Transaminase,SGOT,Aspartate Apoaminotransferase,Glutamate-Aspartate Transaminase,L-Aspartate-2-Oxoglutarate Aminotransferase,Serum Glutamic-Oxaloacetic Transaminase,Aminotransferase, Aspartate,Aminotransferase, L-Aspartate-2-Oxoglutarate,Aminotransferases, Aspartate,Apoaminotransferase, Aspartate,Glutamate Aspartate Transaminase,Glutamic Oxaloacetic Transaminase,Glutamic-Oxaloacetic Transaminase, Serum,L Aspartate 2 Oxoglutarate Aminotransferase,Serum Glutamic Oxaloacetic Transaminase,Transaminase, Aspartate,Transaminase, Glutamate-Aspartate,Transaminase, Glutamic-Oxaloacetic,Transaminase, Serum Glutamic-Oxaloacetic
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries

Related Publications

A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
June 2023, Drug research,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
January 2019, Annals of transplantation,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
December 2013, Canadian journal of physiology and pharmacology,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
July 2013, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
September 2005, The Journal of surgical research,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
June 1995, Transplantation,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
October 2022, European journal of histochemistry : EJH,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
January 2000, Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
November 2015, Journal of hepatology,
A Iannelli, and G de Sousa, and N Zucchini, and L Peyre, and J Gugenheim, and R Rahmani
January 2013, PloS one,
Copied contents to your clipboard!