Pyruvate Is Superior to Citrate in Oral Rehydration Solution in the Protection of Intestine via Hypoxia-Inducible Factor-1 Activation in Rats With Burn Injury

Abstract

Background: Recent studies have suggested that pyruvate-enriched oral rehydration solution (Pyr-ORS) may be superior to the standard bicarbonate-based ORS in the protection of intestine from ischemic injury. The aim of this study was to compare the effects of Pyr-ORS with citrate-enriched ORS (Cit-ORS) on the intestinal hypoxia-inducible factor-1 (HIF-1)–erythropoietin (EPO) signaling pathway for enteral rehydration in a rat model of burn injury. Methods: Rats were randomly assigned to 4 groups (N = 20, 2 subgroups each: n = 10): scald sham (group SS), scald with no fluid resuscitation (group SN), scald and resuscitation with enteral Cit-ORS (group SC), and scald and resuscitation with enteral Pyr-ORS (group SP). At 2.5 and 4.5 hours after a 35% total body surface area (TBSA) scald, intestinal mucosal blood flow (IMBF), contents of HIF-1, EPO, endothelial nitric oxide synthase (eNOS), nitric oxide (NO), barrier protein (ZO-1), levels of serum diamine oxidase (DAO), and intestinal mucosal histology injury score were determined. Results: Serum DAO activities in the scalded groups were significantly elevated, but less raised in group SP than in group SC, at 2.5 hours and at 4.5 hours after the scald. Further, group SP more profoundly preserved intestinal HIF-1 expression compared with group SC at the 2 time points. Compared with group SC, group SP had markedly elevated intestinal EPO, eNOS, and NO levels at the same time points, respectively (P < .05). Similarly, IMBF and ZO-1 levels were significantly higher in group SP than in group SC. Intestinal mucosal histopathological scores were statistically higher at 2.5 hours and 4.5 hours after scalding but were more attenuated in group SP than in group SC (P < .05). Immunofluorescence expression of intestinal mucosal ZO-1 was consistent with the above changes. The above parameters were also significantly different between groups SC and SN (all P < .05). Conclusion: Pyr-ORS provides a superior option to Cit-ORS for the preservation of intestinal blood flow and barrier function and the attenuation of histopathological alterations in enteral resuscitation of rats with burn injury. Its underlying mechanism may be closely related to the pyruvate in activation of intestinal HIF-1-EPO signaling cascades.

Keywords

burns erythropoietin intestinal mucosal blood flow hypoxia inducible factor-1 oral rehydration solution pyruvate ZO-1

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References

Cancio

Kramer

Hoskins

. Gastrointestinal fluid resuscitation of thermally injured patients. J Burn Care Res. 2006;27:561-569.

Michael

Oliveira

Kinsky

. Enteral resuscitation of burn shock using World Health Organization oral rehydration solution: a potential solution for mass casualty care. J Burn Care Res. 2006;27:819-825.

Milner

Greenough

III Asuku

. From cholera to burns: a role for oral rehydration therapy. J Health Popul Nutr. 2011;6:648-651.

Matheson

Wilson

Garrison

. Regulation of intestinal blood flow. J Surg Res. 2000;93:182-196.

Kawano

Tsuji

. Role of mucosal blood flow: a conceptional review in gastric mucosal injury and protection. J Gastroenterol Hepatol. 2000;15(suppl):D1-D6.

Beleslin-Cokic

Cokic

Weksler

Schechter

Noguchi

. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood. 2004;104:2073-2080.

Brix

Mesters

Pellerin

Jöhren

. Endothelial cell-derived nitric oxide enhances aerobic glycolysis in astrocytes via HIF-1α-mediated target gene activation. J Neurosci. 2012;32:9727-9735.

Furuta

Turner

Taylor

. Hypoxia-inducible factor 1–dependent induction of intestinal Trefoil factor protects barrier function during hypoxia. J Exp Med. 2001;193:1027-1034.

Forbes

Verma

. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 2002;277:23111-23115.

10.

Ryou

Liu

Ren

Sun

Mallet

Yang

. Pyruvate protects the brain against ischemia-reperfusion injury by activating the erythropoietin signaling pathway. Stroke. 2012;43:1101-1107.

11.

Ren

Liu

Song

Zhai

. A novel specific application of pyruvate protects the mouse retina against white light damage: differential stabilization of HIF-1α and HIF-2α. Invest Ophthalmol Vis Sci. 2011;52:3112-3118.

12.

Luo

. Pyruvate is superior to reverse visceral hypoperfusion in peritoneal resuscitation from hemorrhagic shock in rats. Shock. 2014;41:355-361.

13.

Petrat

Rönn

de Groot

. Protection by pyruvate infusion in a rat model of severe intestinal ischemia-reperfusion injury. J Surg Res. 2011;167:e93-e101.

14.

Jiang

Zhou

. Pyruvate improves neutrophilic nitric oxide generation in peritoneal dialysis solutions. Artif Organs. 2005;29:976-980.

15.

Gou

Tan

Cai

Zhou

. Pyruvate effects on red blood cells during in vitro cardiopulmonary bypass with dogs’ blood. Artif Organs. 2012;36:988-991.

16.

Liu

Zhao

. Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns. Burns. 2014;40:693-701.

17.

Xie

. Pyruvate oral rehydration solution improved visceral function and survival in shock rats. J Surg Res. 2015;193:344-354.

18.

Islam

. Citrate can effectively replace bicarbonate in oral rehydration salts for cholera and infantile diarrhoea. Bull World Health Organ. 1986;64:145-150.

19.

Chiu

McArdle

Brown

Scott

Gurd

. Intestinal mucosal lesion in low-flow states, I: a morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 1970;101:478-483.

20.

Hassoun

Kone

Mercer

Moody

Weisbrodt

Moore

. Post-injury multiple organ failure: the role of the gut. Shock. 2001;15:1-10.

21.

Puleo

Arvanitakis

Van Gossum

Preiser

. Gut failure in the ICU. Semin Respir Crit Care Med. 2011;32:626-638.

22.

Sharma

Mongan

. Hypertonic sodium pyruvate solution is more effective than Ringer’s ethyl pyruvate in the treatment of hemorrhagic shock. Shock. 2010;33:532-540.

23.

Borle

Stanko

. Pyruvate reduces anoxic injury and free radical formation in perfused rat hepatocytes. Am J Physiol. 1996;270:G535-G540.

24.

Flaherty

Hoxha

Sun

. Pyruvate-fortified fluid resuscitation improves hemodynamic stability while suppressing systemic inflammation and myocardial oxidative stress after hemorrhagic shock. Mil Med. 2010;175:166-172.

25.

Bai

Liu

. Pyruvate Ringer’s solution corrects lactic acidosis and prolongs survival during hemorrhagic shock in rats. J Emerg Med. 2013;45:885-893.

26.

Olivencia-Yurvati

Blair

Baig

Mallet

. Pyruvate-enhanced cardioprotection during surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2003;17:715-720.

27.

Schillinger

Hünlich

Sossalla

Hermann

Hasenfuss

. Intracoronary pyruvate in cardiogenic shock as an adjunctive therapy to catecholamines and intra-aortic balloon pump shows beneficial effects on hemodynamics. Clin Res Cardiol. 2011;100:433-438.

28.

Ryou

Flaherty

Hoxha

. Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass. Am J Physiol Heart Circ Physiol. 2009;297:H1914-H1922.

29.

Dalgard

Mohyeldin

Verma

. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors. Biochem J. 2004;380:419-424.

30.

Koivunen

Hirsilä

Remes

Hassinen

Kivirikko

Myllyharju

. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem. 2007;282:4524-4532.

31.

Kannan

Colorado

Reino

. Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2011;300:G853-G861.

32.

Matheson

Wilson

Garrison

. Regulation of intestinal blood flow. J Surg Res. 2000;93:182-196.

33.

deMuinck

Zhuang

. Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve. Proc Natl Acad Sci U S A. 2005;102:10999-11004.

34.

Kang

Zhou

. Effects of pyruvate-enriched peritoneal dialysis solution on intestinal barrier in peritoneal resuscitation from hemorrhagic shock in rats. J Surg Res. 2015;193:368-376.

35.

Rosenberger

Khoury

Kong

Weissmüller

Robinson

Colgan

. Identification of vasodilator-stimulated phosphoprotein (VASP) as an HIF-regulated tissue permeability factor during hypoxia. FASEB J. 2007;21:2613-2621.

36.

Jackevicius

Fan

Warner

. Clinical outcomes of erythropoietin use in heart failure patients with anemia of chronic kidney disease. J Card Fail. 2014;20:327-333.

37.

Robertson

Hannay

Yamal

. Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA. 2014;312:36-47.

38.

Kristo

Yoshimura

Niu

. The intermediary metabolite pyruvate attenuates stunning and reduces infarct size in in vivo porcine myocardium. Am J Physiol Heart Circ Physiol. 2004;286:H517-H524.

39.

Liepinsh

Makrecka

Kuka

. The heart is better protected against myocardial infarction in the fed state compared to the fasted state. Metabolism. 2014;63:127-136.

40.

Fukushima

Lee

Moro

Hovda

Sutton

. Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury. J Neurotrauma. 2009;26:1095-1110.

41.

Keely

Campbell

Baird

. Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis. Mucosal Immunol 2014;7:114-123.

42.

Shiou

Chen

. Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis. J Biol Chem. 2011;286:12123-12132.

43.

Fowler

Fletcher

Fischer

II . Caring for critically ill patients with ebola virus disease: perspectives from west Africa. Am J Respir Crit Care Med. 2014;190:733-737.

44.

Hiremath

Akbari

Shabana

Fergusson

Knoll

. Prevention of contrast-induced acute kidney injury: is simple oral hydration similar to intravenous? A systematic review of the evidence. PloS One. 2013;8:e60009.

45.

Schödel

Klanke

Weidemann

. HIF-prolyl hydroxylases in the rat kidney: physiologic expression patterns and regulation in acute kidney injury. Am J Physiol. 2009;174:1663-1674.

46.

Olek

Kujach

Wnuk

Laskowski

. Single sodium pyruvate ingestion modifies blood acid-base status and post-exercise lactate concentration in humans. Nutrients. 2014;6:1981-1992.

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