BACKGROUND: The aim of the present study was to evaluate the effect of donor pretreatment with atorvastatin on ischemia/reperfusion (I/R) injury in renal transplantation in rats. METHODS: Donor rats were pretreated orally with atorvastatin or vehicle 2 days prior to explantation. Kidneys were stored for 24 hr at 4 degrees C in University of Wisconsin solution and transplanted into isogeneic or allogeneic recipients. RESULTS: Donor treatment with atorvastatin improved initial graft function, reduced renal inflammation, and the number of TUNEL-positive cells in renal tissue after prolonged cold storage and isogeneic transplantation. In the allogeneic transplantation model, donor treatment with atorvastatin reduced renal inflammation in grafts harvested after 5 days, but no improvement of long-term graft survival (24 weeks) could be observed. A genome wide gene expression profile of donor kidneys from atorvastatin treated or vehicle treated rats revealed a fivefold downregulation of aldose reductase in all atorvastatin treated animals (P<0.01). Donor treatment with an aldose-reductase inhibitor improved kidney function and reduced renal inflammation after prolonged cold storage and isogeneic transplantation. CONCLUSION: Our data suggest that downregulation of aldose reductase in renal tissue might underlie the protective effect of donor atorvastatin treatment. Donor pretreatment with a statin or an aldose reductase inhibitor could offer a new treatment strategy to prevent transplantation associated tissue injury.
BACKGROUND: The aim of the present study was to evaluate the effect of donor pretreatment with atorvastatin on ischemia/reperfusion (I/R) injury in renal transplantation in rats. METHODS:Donorrats were pretreated orally with atorvastatin or vehicle 2 days prior to explantation. Kidneys were stored for 24 hr at 4 degrees C in University of Wisconsin solution and transplanted into isogeneic or allogeneic recipients. RESULTS:Donor treatment with atorvastatin improved initial graft function, reduced renal inflammation, and the number of TUNEL-positive cells in renal tissue after prolonged cold storage and isogeneic transplantation. In the allogeneic transplantation model, donor treatment with atorvastatinreduced renal inflammation in grafts harvested after 5 days, but no improvement of long-term graft survival (24 weeks) could be observed. A genome wide gene expression profile of donor kidneys from atorvastatin treated or vehicle treated rats revealed a fivefold downregulation of aldose reductase in all atorvastatin treated animals (P<0.01). Donor treatment with an aldose-reductase inhibitor improved kidney function and reduced renal inflammation after prolonged cold storage and isogeneic transplantation. CONCLUSION: Our data suggest that downregulation of aldose reductase in renal tissue might underlie the protective effect of donoratorvastatin treatment. Donor pretreatment with a statin or an aldose reductase inhibitor could offer a new treatment strategy to prevent transplantation associated tissue injury.
Authors: F Cicora; J Roberti; D Vasquez; D Guerrieri; N Lausada; P Cicora; G Palti; E Chuluyan; P Gonzalez; P Stringa; C Raimondi Journal: Clin Exp Immunol Date: 2012-01 Impact factor: 4.330
Authors: Clotilde Fuentes-Orozco; Sara Jazmín Garcia-Salazar; Benjamín Gómez-Navarro; Eduardo González-Espinoza; Alonso Zepeda-González; Juan Narciso Ramírez-Robles; Rafael Castañeda-Espinoza; Irinea Yáñez-Sánchez; Francisco Javier Gálvez-Gastelum; Gabino Cervantes-Guevara; Guillermo Alonso Cervantes-Cardona; Guadalupe Ivette Contreras-Hernández; Jacob Esau Pérez-Landeros; David García-Martinez; Alejandro González-Ojeda Journal: Ann Transplant Date: 2018-06-29 Impact factor: 1.530