The Effect of Ethyl Pyruvate on Oxidative Stress in Intestine and Bacterial Translocation After Thermal Injury

Karabeyoğlu, Melih; Ünal, Bülent; Bozkurt, Birkan; Dolapçı, İştar; Bi̇lgi̇han, Ayşe; Karabeyoğlu, I; Cengiz, Ümer

doi:10.1016/j.jss.2007.02.050

Cited by 36 publications

(29 citation statements)

References 38 publications

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“…Treatment with EP has been shown to improve survival and alleviate organ dysfunction in a wide variety of preclinical models of critical illness (19,20) including the amelioration of IRI in organs (13,34,77,84) including the kidney (13). For instance, Chung et al (13) demonstrated that EP improved serum creatinine after IRI in rats, although HMGB1 mRNA expression remained unchanged.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 in renal ischemic injury

Rabadi

Ghaly

Goligorksy

et al. 2012

American Journal of Physiology-Renal Physiology

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Factors that initiate cellular damage and trigger the inflammatory response cascade and renal injury are not completely understood after renal ischemia-reperfusion injury (IRI). High-mobility group box-1 protein (HMGB1) is a damage-associated molecular pattern molecule that binds to chromatin, but upon signaling undergoes nuclear-cytoplasmic translocation and release from cells. Immunohistochemical and Western blot analysis identified HMGB1 nuclear-cytoplasmic translocation and release from renal cells (particularly vascular and tubular cells) into the venous circulation after IRI. Time course analysis indicated HMGB1 release into the venous circulation progressively increased parallel to increased renal ischemic duration. Ethyl pyruvate (EP) treatment blocked H2O2(oxidative stress)-induced HMGB1 release from human umbilical vein endothelial cells in vitro, and in vivo resulted in nuclear retention and significant blunting of HMGB1 release into the circulation after IRI. EP treatment before IRI improved short-term serum creatinine and albuminuria, proinflammatory cyto-/chemokine release, and long-term albuminuria and fibrosis. The renoprotective effect of EP was abolished when exogenous HMGB1 was injected, suggesting EP's therapeutic efficacy is mediated by blocking HMGB1 translocation and release. To determine the independent effects of circulating HMGB1 after injury, exogenous HMGB1 was administered to healthy animals at pathophysiological dose. HMGB1 administration induced a rapid surge in systemic circulating cyto-/chemokines (including TNF-α, eotaxin, G-CSF, IFN-γ, IL-10, IL-1α, IL-6, IP-10, and KC) and led to mobilization of bone marrow CD34+Flk1+ cells into the circulation. Our results indicate that increased ischemic duration causes progressively enhanced HMGB1 release into the circulation triggering damage/repair signaling, an effect inhibited by EP because of its ability to block HMGB1 nuclear-cytoplasmic translocation.

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Section: Discussionmentioning

confidence: 99%

HMGB1 in renal ischemic injury

Rabadi

Ghaly

Goligorksy

et al. 2012

American Journal of Physiology-Renal Physiology

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“…in many organs (33,98,244,265). Ethyl pyruvate is also an effective scavenger of oxygen radicals (39,104,237).…”

Section: Hmgb1 Oxidative Stress and Diseasementioning

confidence: 99%

High-Mobility Group Box 1, Oxidative Stress, and Disease

Tang

Kang

Zeh

et al. 2011

Antioxidants & Redox Signaling

426

363

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Oxidative stress and associated reactive oxygen species can modify lipids, proteins, carbohydrates, and nucleic acids, and induce the mitochondrial permeability transition, providing a signal leading to the induction of autophagy, apoptosis, and necrosis. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and downstream apoptosis or survival. Accumulation of HMGB1 at sites of oxidative DNA damage can lead to repair of the DNA. As a redox-sensitive protein, HMGB1 contains three cysteines (Cys23, 45, and 106). In the setting of oxidative stress, it can form a Cys23-Cys45 disulfide bond; a role for oxidative homo-or heterodimerization through the Cys106 has been suggested for some of its biologic activities. HMGB1 causes activation of nicotinamide adenine dinucleotide phosphate oxidase and increased reactive oxygen species production in neutrophils. Reduced and oxidized HMGB1 have different roles in extracellular signaling and regulation of immune responses, mediated by signaling through the receptor for advanced glycation end products and=or Toll-like receptors. Antioxidants such as ethyl pyruvate, quercetin, green tea, N-acetylcysteine, and curcumin are protective in the setting of experimental infection=sepsis and injury including ischemia-reperfusion, partly through attenuating HMGB1 release and systemic accumulation. Antioxid. Redox Signal. 14, 1315-1335.

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“…Intestinal ischemia-reperfusion results in organ injury through both tissue hypoxia and reperfusion phenomena mediated by inflammatory response and oxidative stress [9,10] . There is increasing evidence that the inflammatory response and oxidative stress in the small intestine exert important roles in the bacteria or endotoxin translocation and the development of SIRS after thermal injury [11][12][13][14][15] . Evidence has indicated that endogenous carbon monoxide (CO), a biproduct of inducible heme oxygenase can modulates inflammation.…”

Section: Introductionmentioning

confidence: 99%

Suppression of inflammatory cytokine production and oxidative stress by CO-releasing moleculesliberated CO in the small intestine of thermally-injured mice¹

Liu

Sun

et al. 2008

Acta Pharmacologica Sinica

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Aim: To determine whether carbon monoxide (CO)-releasing molecules-liberated CO suppress inflammatory cytokine production and oxidative stress in the small intestine of burnt mice. Methods: Twenty-eight mice were assigned to 4 groups. The mice in the sham group (n=7) underwent sham thermal injury, whereas the mice in the burn group (n=7) received 15% total body surface area full-thickness thermal injury, the mice in the burn+CO-releasing molecules (CORM)-2 group (n=7) underwent the same injury with immediate administration of CORM-2 (8 mg/kg, iv), and the mice in the burn+inactivated CORM (iCORM)-2 group (n=7) underwent the same injury with immediate administration of iCORM-2. The levels of inflammatory cytokines in the tissue homogenates were measured by ELISA. The levels of malondialdehyde (MDA), nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in the small intestine were also assessed. In the in vitro experiment, Caco-2 cells were stimulated by experimental mouse sera (50%, v/v) for 4 h. Subsequently, the levels of interleukin (IL)-8 and NO in the supernatants were assessed. Reactive oxygen species (ROS) generation in Caco-2 cells was also measured. Results: The treatment of burnt mice with CORM-2 significantly attenuated the levels of IL-1β, TNF-α, MDA, and NO in tissue homogenates. This was accompanied by a decrease of iNOS expression. In parallel, the levels of IL-8, NO, and intracellular ROS generation in the supernatants of Caco-2 stimulated by the CORM-2-treated burnt mouse sera was markedly decreased. Conclusion: CORM-released CO attenuates the production of inflammatory cytokines, prevents burn-induced ROS generation, and suppresses the oxidative stress in the small intestine of burnt mice by interfering with the protein expression of iNOS.

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The Effect of Ethyl Pyruvate on Oxidative Stress in Intestine and Bacterial Translocation After Thermal Injury

Cited by 36 publications

References 38 publications

HMGB1 in renal ischemic injury

HMGB1 in renal ischemic injury

High-Mobility Group Box 1, Oxidative Stress, and Disease

Suppression of inflammatory cytokine production and oxidative stress by CO-releasing moleculesliberated CO in the small intestine of thermally-injured mice¹

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The Effect of Ethyl Pyruvate on Oxidative Stress in Intestine and Bacterial Translocation After Thermal Injury

Cited by 36 publications

References 38 publications

HMGB1 in renal ischemic injury

HMGB1 in renal ischemic injury

High-Mobility Group Box 1, Oxidative Stress, and Disease

Suppression of inflammatory cytokine production and oxidative stress by CO-releasing moleculesliberated CO in the small intestine of thermally-injured mice1

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Suppression of inflammatory cytokine production and oxidative stress by CO-releasing moleculesliberated CO in the small intestine of thermally-injured mice¹