Role of Akt-Dependent Pathway in Resveratrol-Mediated Cardioprotection after Trauma-Hemorrhage

Tsai, Yung-Fong; Liu, Fu-Chao; Lau, Ying-Tung; Yu, Huang-Ping

doi:10.1016/j.jss.2011.05.039

Cited by 28 publications

(34 citation statements)

References 41 publications

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“…We hypothesized that agents that improve mitochondrial function may promote cellular function and extend life following hemorrhagic injury. In previous studies, our laboratory and others have observed improved organ function in rats treated with resveratrol following hemorrhagic injury (23,30). Resveratrol, a phytochemical, is a naturally occurring antioxidant and free radical scavenger.…”

Section: Discussionmentioning

confidence: 93%

Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Ayub

Poulose

Raju

2015

Mol Med

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Resveratrol has been shown to potentiate mitochondrial function and extend longevity; however, there is no evidence to support whether resveratrol can improve survival or prolong life following hemorrhagic shock. We sought to determine whether (a) resveratrol can improve survival following hemorrhage and resuscitation and (b) prolong life in the absence of resuscitation. Using a hemorrhagic injury (HI) model in the rat, we describe for the first time that the naturally occurring small molecule, resveratrol, may be an effective adjunct to resuscitation fluid. In a series of three sets of experiments we show that resveratrol administration during resuscitation improves survival following HI (p < 0.05), resveratrol and its synthetic mimic SRT1720 can significantly prolong life in the absence of resuscitation fluid (<30 min versus up to 4 h; p < 0.05), and resveratrol as well as SRT1720 restores left ventricular function following HI. We also found significant changes in the expression level of mitochondria-related transcription factors Ppar-α and Tfam, as well as Pgc-1α in the left ventricular tissues of rats subjected to HI and treated with resveratrol. The results indicate that resveratrol is a strong candidate adjunct to resuscitation following severe hemorrhage.

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Section: Discussionmentioning

confidence: 93%

Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Ayub

Poulose

Raju

2015

Mol Med

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“…Resveratrol has also been shown to be beneficial in several trauma-hemorrhage models. Resuscitation with resveratrol not only improves cardiac output (14), it has been shown to decrease hepatic injury and inflammation following hemorrhagic shock (15). As such, resveratrol may provide a useful therapeutic adjunct to standard fluid resuscitation following traumatic injury.…”

Section: Discussionmentioning

confidence: 99%

“…Resveratrol may also have antioxidant effects through a variety of complementary mechanisms, including the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor, which induce antioxidant and drug-metabolizing enzymes. When used in animal models of hemorrhagic shock, RSV has been shown to reduce inflammation and mitigate organ dysfunction (14, 15). There is little information, however, on the impact of RSV on mitochondrial function following acute blood loss.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

Wang¹,

Guan²,

Karamercan³

et al. 2015

Shock

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Objective Hemorrhagic shock may contribute to acute kidney injury 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. Method Using a decompensated hemorrhagic shock model, male Long-Evans rats (n=6 per group) were sacrificed prior to hemorrhage (Sham), at severe shock, and following either lactated Ringer’s (LR) Resuscitation or LR+RSV Resuscitation (RSV: 30mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen (BUN) and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (CI, CII, and CIV) using high-resolution respirometry. Total mitochondria reactive oxygen species (ROS) were measured using fluorometry and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. qPCR was used quantify mRNA from PGC1-α, SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results RSV supplementation during resuscitation restored mitochondrial respiratory capacity, decreased mitochondrial ROS and lipid peroxidation. Compared to standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both SOD2 and catalase expression. Although RSV was associated with decreased lactate production, pH, BUN 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.

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“…Animals were then resuscitated with four times the shed volume in LR solution with or without RSV (30 mg/kg, 50 mg/mL in 50% DMSO, Orchid Pharmaceuticals, Lalilab, Durham NC) over 60 minutes. 14–16,19 Animals (n = 6 per group) were killed before hemorrhage (sham), at severe shock, following LR resuscitation or RSV + LR resuscitation (LR + RSV), 18 hours after LR resuscitation (18hr LR) or LR + RSV resuscitation (18hr LR + RSV). Before sacrifice, blood samples were taken and assayed for arterial blood gases, lactate, and hemoglobin (i-STAT, Abbot Point of Care Inc., Princeton, NJ).…”

Section: Methodsmentioning

confidence: 99%

Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock

Wang

Guan

Widlund

et al. 2014

Journal of Trauma and Acute Care Surgery

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BACKGROUND Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. METHODS With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer’s solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model Assessment–Insulin Resistance index was used to quantify insulin resistance. RESULTS RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 ± 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer’s solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 ± 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 ± 56.6 ng/mL vs. 187.3 ± 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model Assessment–Insulin Resistance index (1.30 ± 0.42 vs. 4.18 ± 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. CONCLUSION Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion.

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Role of Akt-Dependent Pathway in Resveratrol-Mediated Cardioprotection after Trauma-Hemorrhage

Cited by 28 publications

References 41 publications

Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock

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