AKI - Experimental

Kubra Kaynar 2 3 10 13 14 17 19 22 25 28 31 32 37 38 Kubra Kaynar 1 2 9 12 14 16 19 21 18 27 30 32 36 38 Safak Ersoz 0 2 11 14 15 19 20 26 29 32 35 38 Rezzan Aliyazioglu 2 7 14 18 19 24 32 34 38 40 Aysegul Uzun 2 6 14 19 23 32 33 38 39 Sukru Ulusoy 2 5 14 19 32 38 Sait Al 2 4 14 19 32 38 Gulsum Ozkan 2 8 14 19 32 38 Muammer Cansiz 2 8 14 19 32 38 0 Hpital Europen Georges Pompidou, Paris, France 1 Inserm Umrs872, Team 1, Paris, France 2 Jean-Philippe Bertocchio 3 Inserm Umrs872 Team 1, Paris, France 4 Veterinerian Dr., Department of Surgery Research Center, School of Medicine, Karadeniz Technical University 5 Professor Dr., Department of Nephrology, School of Medicine, Karadeniz Technical University. 6 Assistant Professor Dr., Department of Biochemistry; School of Medicine, Karadeniz Technical University. 7 Chu Hpital Maison Blanche, Reims, France 8 Assistant Professor Dr., Department of Nephrology, School of Medicine, Karadeniz Technical University 9 Division of Nephrology, Department of Internal Medicine, University of Michigan , Ann Arbor, USA 10 Division of Nephrology, Department of Internal Medicine, University Hospital Essen , Essen, Germany 11 Morphology Department 12 Universidade Federal de So Paulo 13 Federal University of So Paulo (Unifesp) 14 Jose-Miguel Lpez-Novoa 15 Belozersky Institute of Physico-Chemical Biology, Moscow State University 16 Conway Institute of Biomolecular and Biomedical Sciences, University College , Dublin, Ireland 17 University , Salamanca, Spain 18 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University , Moscow, Russia 19 Erlangen-Nuremberg, Erlangen, Germany 20 Institute of Nephropathology, University of Erlangen-Nuremberg , Erlangen, Germany 21 Institute of Microbiology, University of 22 Medical Clinic 4 - Nephrology and Hypertension, University of Erlangen-Nuremberg , Erlangen, Germany 23 Nephrology Unit, Dept of Biomedical Sciences, University of Foggia , Italy 24 Dept. of Nephrology, University Medical Center , Leiden, The Netherlands 25 Belozersky Institute, Lomonosov Moscow State University , Moscow, Russia 26 Department of Anatomy, College of Medicine,The Catholic University of Korea , Seoul, Republic of Korea 27 Department of Internal Medicine, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea 28 Department of Anatomy, College of Medicine, The Catholic University of Korea , Seoul, Republic of Korea 29 Veterinary Medicine, University of Bologna , Italy 30 Nephrology Dialysis and Hypertension, Policlinico S.Orsola Malpighi , Bologna, It 31 Deis, University of Bologna , Italy 32 Christina Rebecca Scherbaum 33 Nephrology, Dialysis and Hypertension, S.Orsola-Malpighi University Hospital , Bologna, Italy 34 Experimental Medicine, Bicocca University of Milano , Italy 35 Unidad de Toxicologa and Unidad de Fisiopatologa Renal Y Cardiovascular. Universidad de Salamanca. Spain 36 School of Pharmacy, National Defense Medical Center , Taipei, Taiwan 37 Tri-Service General Hospital, National Defense Medical Center , Taipei, Taiwan 38 Sandra M. Sancho-Martinez 39 Instituto de Estudios de Ciencias de la Salud de Castilla Y Len (Iecscyl), Hospital Universitario de Salamanca , Spain 40 University of Salamanca , Salamanca, Spain , Introduction and Aims: Tacrolimus, is widely used in organ transplantations; however there are also several clinical side effects like nephrotoxicity and pancreas toxicity. In addition to its use in renal anaemia, with increasing evidence Erythropoietin (Epo) has been reported to have broader functions independent of its effects on erythropoiesis. Receptors of Epo is expressed in multiple tissues including glomerular, mesangial and tubular epithelial cells in human, rat and mouse kidneys, pancreatic islet cells. Pentoxifylline (Ptx) is a non-selective inhibitor of cyclic-3', The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: - 5-phosphodiesterase (PDE), exhibiting anti-inflammatory properties by inhibiting cytokine production, anti-oxidant properties by preventing release of superoxide and hydrogen-peroxide ions. The aim of this study was to explore effects of erythropoietin and pentoxifylline in tacrolimus-induced pancreatic beta cell and renal injury in rats. Methods: Rats in group I were given saline; rats in group II were injected with tacrolimus; rats in group III were received erythropoietin (Epo) and tacrolimus; while rats in group IV were injected pentoxifylline (Ptx) plus tacrolimus for 9 days. On 10th day, blood and tissue samples were taken for biochemical and pathological evaluations. Results: Tacrolimus injected animals exhibited significant elevation in BUN, serum BUN levels were improved in rats pretreated with Ptx ( table 1). Significantly more apoptotic nuclei were observed in kidneys of tacrolimus group. In rats, subjected to tacrolimus and pretreated with Epo, there was significant decrease in apoptotic nuclei staining than those in tacrolimus group. Blood trough levels of tacrolimus were significantly higher in erythropoietin pretreated group although same amount of tacrolimus was injected with other groups. Conclusions: Results of our study demonstrated significant anti-apoptotic effects of erythropoietin on renal tubules, increasing effect of erythropoietin on tacrolimus blood levels, insignificant anti-oxidant effects of both erythropoietin and pentoxifylline on renal and pancreas tissues. There was no protective effect of Ptx on tacrolimus induced renal toxicity. In order to more fully describe the tacrolimus, Epo and Ptx treatment effects, a tacrolimus dose ranging study with a greater range of tacrolimus concentrations may more fully reveal treatment effects on pancreas and renal injury. IS VASCULAR SMOOTH MUSCLE CELLS MINERALOCORTICOID RECEPTOR INVOLVED IN CYCLOSPORINE A NEPHROTOXICITY? Introduction and Aims: Cyclosporine A (CsA) nephrotoxicity is one of the most frequent adverse event of CsA treatment but its pathophysiology remains unclear. Pharmacological antagonism of the Mineralocorticoid Receptor (MR) has been reported to prevent CsA nephrotoxicity in rat by modulating the expression of vasoactive factors (Perez-Rojas et al. AJPRP 2005). We have recently shown that MR is expressed in the endothelial and vascular smooth muscle cells (VSMC) of renal vasculature (Nguyen Dinh Cat et al. FASEB J 2010). Moreover genetic manipulations of MR expression in the endothelium (Nguyen Dinh Cat et al. FASEB J 2010) or the smooth muscle (unpublished data) alter vascular function. Our working hypothesis is: activation of vascular MR plays a key role in CsA nephrotoxicity. Methods: We studied the effects of pharmacological MR antagonism on acute CsA nephrotoxicity in wild-type female mice fed with low salt diet: control, Ctrl (vehicle), CsA (CsA 100mg/kg/d subcutaneously) and CsA+Can (CsA + canrenoate 30mg/kg/d in tap water). Mice were treated during 10 da (...truncated)