Hao Wang1, Yuxia Guan, Mehmet Akif Karamercan, Lan Ye, Tricia Bhatti, Lance B Becker, Joseph A Baur, Carrie A Sims. 1. *Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China; †The Trauma Center at Penn and ‡The Center for Resuscitation Science, University of Pennsylvania, Philadelphia, Pennsylvania; §Department of Emergency Medicine, Gazi University School of Medicine, Ankara, Turkey; and ∥Institute for Diabetes, Obesity, and Metabolism and Department of Physiology, Perelman School of Medicine, University of Pennsylvania; and ¶Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Abstract
OBJECTIVE: Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. METHODS: Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer's (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. RESULTS: Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood urea nitrogen, and serum creatinine values did not differ between resuscitation strategies. CONCLUSIONS: Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock.
OBJECTIVE:Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. METHODS: Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer's (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood ureanitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. RESULTS:Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood ureanitrogen, and serum creatinine values did not differ between resuscitation strategies. CONCLUSIONS: Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock.
Authors: Julie St-Pierre; Stavit Drori; Marc Uldry; Jessica M Silvaggi; James Rhee; Sibylle Jäger; Christoph Handschin; Kangni Zheng; Jiandie Lin; Wenli Yang; David K Simon; Robert Bachoo; Bruce M Spiegelman Journal: Cell Date: 2006-10-20 Impact factor: 41.582
Authors: Glenn M Chertow; Elisabeth Burdick; Melissa Honour; Joseph V Bonventre; David W Bates Journal: J Am Soc Nephrol Date: 2005-09-21 Impact factor: 10.121
Authors: Joseph P Minei; Joseph Cuschieri; Jason Sperry; Ernest E Moore; Michael A West; Brian G Harbrecht; Grant E O'Keefe; Mitchell J Cohen; Lyle L Moldawer; Ronald G Tompkins; Ronald V Maier Journal: Crit Care Med Date: 2012-04 Impact factor: 7.598
Authors: Anna Csiszar; Nazar Labinskyy; John T Pinto; Praveen Ballabh; Hanrui Zhang; Gyorgy Losonczy; Kevin Pearson; Rafael de Cabo; Pal Pacher; Cuihua Zhang; Zoltan Ungvari Journal: Am J Physiol Heart Circ Physiol Date: 2009-05-08 Impact factor: 4.733
Authors: D L Dyess; R W Powell; A N Swafford; D C Schmacht; W S Roberts; J J Ferrara; J L Ardell Journal: J Pediatr Surg Date: 1994-08 Impact factor: 2.545
Authors: Carrie A Sims; Yuxia Guan; Sarmistha Mukherjee; Khushboo Singh; Paul Botolin; Antonio Davila; Joseph A Baur Journal: JCI Insight Date: 2018-09-06