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Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice
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Jongbloed, Franny
de Bruin, Ron W. F.
Pennings, Jeroen L. A.
Payan-Gomez, Cesar
Engel, Sandra van den
Oostrom, Conny T. van
de Bruin, Alain
Hoeijmakers, Jan H. J.
Steeg, Harry van
IJzermans, Jan N. M.
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2014
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Abstract
Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a different response to fasting, we investigated the effects of preoperative fasting on renal IRI in aged-overweight male and female mice. Male and female F1-FVB/C57BL6-hybrid mice, average age 73 weeks weighing 47.2 grams, were randomized to preoperative ad libitum feeding or 3 days fasting, followed by renal IRI. Body weight, kidney function and survival of the animals were monitored until day 28 postoperatively. Kidney histopathology was scored for all animals and gene expression profiles after fasting were analyzed in kidneys of young and aged male mice. Preoperative fasting significantly improved survival after renal IRI in both sexes compared with normal fed mice. Fasted groups had a better kidney function shown by lower serum urea levels after renal IRI. Histopathology showed less acute tubular necrosis and more regeneration in kidneys from fasted mice. A mRNA analysis indicated the involvement of metabolic processes including fatty acid oxidation and retinol metabolism, and the NRF2-mediated stress response. Similar to young-lean, healthy male mice, preoperative fasting protects against renal IRI in aged-overweight mice of both genders. These findings suggest a general protective response of fasting against renal IRI regardless of age, gender, body weight and genetic background. Therefore, fasting could be a non-invasive intervention inducing increased oxidative stress resistance in older and overweight patients as well. © 2014 Jongbloed et al.
Palabras clave
Glutatión transferasa A2 , Mensajero RNA , Retinol , Factor de transcripción Nrf2 , Distribución de edad , Envejecido , Experimento con animales , Modelo animal , Tejido animal , Peso corporal , Estudio controlado , Cyp4A14 gen D , Restricción de la dieta , Oxidación de ácidos grasos , Gen , Perfiles de expresión génica , Gen Gsta2 , Histopatología , Función del riñón , Lesión renal , Isquemia renal , Necrosis del túbulo renal , Secuencia de nucleótidos , Obesidad , Período preoperatorio , Protección Renal , Lesión por reperfusión , Gen Sc4Mol , Estrés , Tasa de supervivencia , Regeneración de Tejidos , Nivel de urea en sangre , Metabolismo de las vitaminas , Efectos adversos , Ratón C57Bl , Trasplante de riñón , Metabolismo , Obesidad , Estrés oxidativo , Patología , Lesión por reperfusión , Nivel de sangre de nitrógeno ureico , Factores de edad , Nitrógeno ureico en sangre , Redes y vías metabólicas , Ratones endogámicos C57Bl , Exceso de peso , Estrés oxidativo , Lesión por reperfusión
Keywords
Reperfusion Injury , Oxidative Stress , Mice, Inbred C57Bl , Overweight , Blood Urea Nitrogen , Metabolic Networks And Pathways , Age Factors , Urea Nitrogen Blood Level , Reperfusion Injury , Pathology , Oxidative Stress , Obesity , Kidney Transplantation , Metabolism , C57Bl Mouse , Adverse Effects , Vitamin Metabolism , Urea Blood Level , Tissue Regeneration , Survival Rate , Stress , Sc4Mol Gene , Reperfusion Injury , Preoperative Period , Renal Protection , Obesity , Nucleotide Sequene , Kidney Tubule Necrosis , Kidney Ischemia , Kidney Injury , Kidney Function , Histopathology , Gsta2 Gene , Gene Expression Profiling , Gene , Fatty Acid Oxidation , Diet Restriction , Cyp4A14 Dgene , Controlled Study , Body Weight , Animal Tissue , Animal Model , Animal Experiment , Aged , Age Distribution , Urea , Transcription Factor Nrf2 , Messenger Rna , Glutathione Transferase A2
