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Pyruvate Application Indicates an Important Medical Advance

Received: 6 November 2018     Accepted: 3 January 2019     Published: 4 January 2019
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Abstract

On the occasion of the 50th anniversary of WHO-guided oral rehydration salts (ORS) clinical application, this review mainly discussed recent findings in ORS, a novel pyruvate-enriched ORS (Pyr-ORS), in animal experiments. Since past several decades, numerous pieces of evidence have shown that pyruvate owns superior biological and pharmacological characteristics that benefit critical care patients: enhancement of anoxia/hypoxia tolerance, correction of hypoxic lactic acidosis, antagonism of oxidative stress and inflammation, protection of mitochondrial structure and function and anti-apoptosis, etc. Therefore, pyruvate prevents from multi-organ dysfunction and corrects disturbances of glucose metabolism and acid-base balance in patients subjected with various pathogen insults. In recent years, investigations of intravenous pyruvate and oral pyruvate in ORS demonstrated properties above and a double increase of survival in animals subjected to hemorrhagic or burn shock. In the review, biological properties of pyruvate and the high efficiency, underlying mechanisms and vast potential clinical indications of Pyr-ORS were illustrated. The review points out that pyruvate-enriched fluids may be the third generation of fluid therapy, not only a volume expander, but also a therapeutic agent for organ dysfunction and metabolic disturbance; pyruvate may be the first-line drug for fluid therapy: Pyr-ORS becomes the first choice for patients who require fluid rehydration alone or in combination with intravenous pyruvate. Pyruvate applications would improve overall clinical outcomes of various diseases, particularly critical illnesses, potentiating a new most important medical advance this century.

Published in Asia-Pacific Journal of Medicine (Volume 1, Issue 1)
Page(s) 14-20
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Fluid Therapy, Hypoxic Lactic Acidosis, Oral Rehydration Salts, Pyruvate, Resuscitation, Shock

References
[1] Water with sugar and salt. Lancet. 1978; 2:300-1.
[2] Nalin DR, Cash RA. 50 years of oral rehydration therapy: the solution is still simple. Lancet. 2018; 392:536-538.
[3] Glass RI, Stoll BJ. Oral rehydration therapy for diarrheal diseases: A 50-year perspective. JAMA. 2018; 320:865-6.
[4] Wang Y, Huang Y, Yang J, Zhou FQ, Zhao L, Zhou H. Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis. Mil Med Res. 2018; 5:13.
[5] Brooks GA. What does glycolysis make and why is it important? J Appl Physiol (1985). 2010; 108:1450-1.
[6] Dahl NA, Balfour WM. Prolonged anoxic survival due to anoxia pre-exposure: brain ATP, lactate, and pyruvate. Am J Physiol. 1964; 207:452-6.
[7] Borle AB, Stanko RT. Pyruvate reduces anoxic injury and free radical formation in perfused rat hepatocytes. Am J Physiol. 1996; 270:G535-40.
[8] Gou D, Tan H, Cai H, Zhou F. Pyruvate effects on red blood cells during in vitro cardiopulmonary bypass with dogs' blood. Artif Organs. 2012; 36:988-91.
[9] Gupte SA, Wolin MS. Hypoxia promotes relaxation of bovine coronary arteries through lowering cytosolic NADPH. Am J Physiol Heart Circ Physiol. 2006; 290:H2228-38.
[10] Zhou FQ. Advantages of pyruvate over lactate in peritoneal dialysis solutions. Acta Pharmacol Sin. 2001; 22:385-92.
[11] Ryou MG, Liu R, Ren M, Sun J, Mallet RT, Yang SH. Pyruvate protects the brain against ischemia-reperfusion injury by activating the erythropoietin signaling pathway. Stroke. 2012; 43:1101-7.
[12] Hu S, Lin ZL, Zhao ZK, et al. 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. JPEN J Parenter Enteral Nutr. 2016; 40:924-33.
[13] Priestman DA, Orfali KA, Sugden MC. Pyruvate inhibition of pyruvate dehydrogenase kinase. Effects of progressive starvation and hyperthyroidism in vivo, and of dibutyryl cyclic AMP and fatty acids in cultured cardiac myocytes. FEBS Lett. 1996; 393:174-8.
[14] Sharma AB, Sun J, Howard LL, Williams AG Jr, Mallet RT. Oxidative stress reversibly inactivates myocardial enzymes during cardiac arrest. Am J Physiol Heart Circ Physiol. 2007; 292:H198-206.
[15] Kraut JA, Madias NE. Lactic acidosis: current treatments and future directions. Am J Kidney Dis. 2016; 68:473-82.
[16] Broder G, Weil MH. Excess lactate: an index of reversibility of shock in human patients. Science. 1964; 143:1457-9.
[17] Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006; 10:R22.
[18] Mongan PD, Fontana JL, Chen R, Bünger R. Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. Am J Physiol. 1999; 277:H2253-63.
[19] Koustova E, Rhee P, Hancock T, et al. Ketone and pyruvate Ringer’s solutions decrease pulmonary apoptosis in a rat model of severe hemorrhagic shock and resuscitation. Surgery 2003; 134:267–74.
[20] Flaherty DC, Hoxha B, Sun J, et al. Pyruvate-fortified fluid resuscitation improves hemodynamic stability while suppressing systemic inflammation and myocardial oxidative stress after hemorrhagic shock. Mil Med. 2010; 175:166-72.
[21] Hu S, Bai XD, Liu XQ, et al. Pyruvate Ringer's solution corrects lactic acidosis and prolongs survival during hemorrhagic shock in rats. J Emerg Med. 2013; 45:885-93.
[22] Zhou FQ. Pyruvate in the correction of intracellular acidosis: a metabolic basis as a novel superior buffer. Am J Nephrol. 2005; 25:55-63.
[23] 张元芳吴肇光周方强.丙酮酸钠在缺氧型乳酸性酸中毒中的潜在临床应用[J].中华医学杂志. 2015; 95:958-60。
[24] Stacpoole PW, Wright EC, Baumgartner TG, et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N Engl J Med. 1992; 327:1564-9.
[25] Liu R, Wang SM, Liu XQ, et al. Pyruvate alleviates lipid peroxidation and multiple-organ dysfunction in rats with hemorrhagic shock. Am J Emerg Med. 2016; 34:525-30.
[26] Cicalese L, Subbotin V, Rastellini C, Stanko RT, Rao AS, Fung JJ. Preservation injury and acute rejection of rat intestinal grafts: protection afforded by pyruvate. J Gastrointest Surg. 1999; 3:549-54.
[27] 钟莹,张占科,周方强等.极化液和丙酮酸钠联合治疗严重烫伤多器官功能不全综合症大鼠实验研究[J].解放军医药杂志. (with English abstract) 2018; 30:1-6。
[28] Kerr PM, Suleiman MS, Halestrap AP: Reversal of permeability transition during recovery of hearts from ischemia and its enhancement by pyruvate. Am J Physiol. 1999; 276:H496-502.
[29] Sharma P, Walsh KT, Kerr-Knott KA, Karaian JE, Mongan PD. Pyruvate modulates hepatic mitochondrial functions and reduces apoptosis indicators during hemorrhagic shock in rats. Anesthesiology. 2005; 103:65-73.
[30] Varma SD, Chandrasekaran K. High sugar-induced repression of antioxidant and anti-apoptotic genes in lens: reversal by pyruvate. Mol Cell Biochem. 2015; 403:149-58.
[31] Scott GF, Nguyen AQ, Cherry BH, et al. Pyruvate preserves antiglycation defenses in porcine brain after cardiac arrest. Exp Biol Med (Maywood). 2017; 242:1095-103.
[32] Koivisto H, Leinonen H, Puurula M, et al. Corrigendum: Chronic pyruvate supplementation increases exploratory activity and brain energy reserves in young and middle-aged mice. Front Aging Neurosci. 2017; 9:67.
[33] Mallet RT, Olivencia-Yurvati AH, Bünger R, et al. Pyruvate enhancement of cardiac performance: Cellular mechanisms and clinical application. Exp Biol Med (Maywood). 2018; 243:198-210.
[34] Schillinger W, Hünlich M, Sossalla S, Hermann HP, Hasenfuss G. 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; 100:433-8.
[35] Mateva L, Petkova I, Petrov K, et al. Ten-Day course of sodium pyruvate infusions in patients with chronic liver diseases (CLD). Jpn Pharmacol Ther. 1996; 24:2629-39.
[36] Johnson AC, Zager RA. Renal cortical pyruvate as a potentially critical mediator of acute kidney injury. Nephron Clin Pract. 2014; 127:129-32.
[37] Petrat F, Rönn T, de Groot H. Protection by pyruvate infusion in a rat model of severe intestinal ischemia-reperfusion injury. J Surg Res. 2011; 167:e93-101.
[38] Raat NJ, Hilarius PM, Johannes T, de Korte D, Ince C, Verhoeven AJ. Rejuvenation of stored human red blood cells reverses the renal microvascular oxygenation deficit in an isovolemic transfusion model in rats. Transfusion. 2009; 49:427-34
[39] Ing TS, Zhou XJ, Yu AW, Zhou FQ, Vaziri ND. Effects of pyruvate-based or lactate-based peritoneal dialysis solutions on neutrophil intracellular pH. Int J Artif Organs. 1997; 20:255-60.
[40] Petkova I, Hristov V, Petrov K, Thorn W. Oral application of sodium pyruvate in healthy persons and patients with diabetes mellitus type 1. Medecine Clinique 2007; 60:579-84.
[41] Inoue T, Murakami N, Ayabe T, et al. Pyruvate improved insulin secretion status in a mitochondrial diabetes mellitus patient. J Clin Endocrinol Metab. 2016; 101:1924-6.
[42] 季敏,张勇进,周方强.丙酮酸盐用于防治糖尿病视网膜病变[J].中国眼耳鼻喉科杂志. 2008; 8:266-8.
[43] 齐艳秀,符俊达,王玉清,王冬兰.丙酮酸对糖尿病大鼠视网膜氧化损伤及超微结构的影响[J].国际眼科杂志.(with English abstract) 2014; 14:2143-6.
[44] Islam MR. Citrate can effectively replace bicarbonate in oral rehydration salts for cholera and infantile diarrhoea. Bull World Health Organ. 1986; 64:145-50.
[45] Pulungsih SP, Punjabi NH, Rafli K, et al. Standard WHO-ORS versus reduced-osmolarity ORS in the management of cholera patients. J Health Popul Nutr. 2006; 24:107-12.
[46] Milner SM, Greenough WB 3rd, Asuku ME, et al. From cholera to burns: a role for oral rehydration therapy. J Health Popul Nutr. 2011; 29:648-51.
[47] Lamontagne F, Fowler RA, Adhikari NK, et al. Evidence-based guidelines for supportive care of patients with Ebola virus disease. Lancet 2018; 391:700-8.
[48] Hu S, Liu WW, Zhao Y, et al. Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns. Burns. 2014; 40:693-701.
[49] Yu W, Hu S, Xie ZY, et al. Pyruvate oral rehydration solution improved visceral function and survival in shock rats. J Surg Res. 2015; 193:344-54.
[50] Liu R, Hu XH, Wang SM, et al. Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs. Burns. 2016; 42:797-806.
[51] Zhao ZK, Hu S, Zhang LJ, et al. Electroacupuncture at Zusanli (ST36) promotes gastric emptying and mucosal blood flow during oral resuscitation of scalded rats with a pyruvate-enriched ORS. Burns. 2015; 41:575-81.
[52] Liu R, Wang SM, Li ZY, Yu W, Zhang HP, Zhou FQ. Pyruvate in reduced osmolarity oral rehydration salt corrected lactic acidosis in sever scald rats. J Surg Res. 2018; 226:173-80.
[53] Morrison MA, Spriet LL, Dyck DJ. Pyruvate ingestion for 7 days does not improve aerobic performance in well-trained individuals. J Appl Physiol. 2000; 89:549-56.
[54] Olek RA, Luszczyk M, Kujach S, et al. Single pyruvate intake induces blood alkalization and modification of resting metabolism in humans. Nutrition. 2015; 31:466-74.
[55] Wright EM, Loo DD, Hirayama BA, Turk E. Surprising versatility of Na+-glucose cotransporters: SLC5. Physiology (Bethesda). 2004; 19:370-6.
[56] Wright SM, Noon MJ, Greenough WB 3rd. Oral rehydration therapy and feeding replaces total parenteral nutrition: A clinical vignette. J Gen Intern Med. 2016; 31:255-7.
[57] Nakamura M, Uchida K, Akahane M, Watanabe Y, Ohtomo K, Yamada Y. The effects on gastric emptying and carbohydrate loading of an oral nutritional supplement and an oral rehydration solution: a crossover study with magnetic resonance imaging. Anesth Analg. 2014; 118:1268.
[58] Gupta R, Gan TJ. Peri-operative fluid management to enhance recovery. Anaesthesia. 2016; 71 Suppl 1:40-5.
[59] 白卫平,李娟,韩瑞丽等.低渗丙酮酸钠口服补液盐对大鼠窒息性心脏停搏复苏后脑损伤的影响[J].中华损伤与修复杂志.(电子版, with English abstract) 2017; 12:326-30.
[60] Liepinsh E, Makrecka M, Kuka J, et al. The heart is better protected against myocardial infarction in the fed state compared to the fasted state. Metabolism. 2014; 63:127-36.
[61] 刘锟,付玉川,杜美关等.利用高分辨氢质子磁共振波谱技术探讨丙酮酸钠对反复严重低血糖新生大鼠枕叶皮层的保护作用及其机制[J].中华围产医学杂志.(with English abstract) 2017; 20:228-33.
[62] Walker SK, Matheson PJ, Schreiner MT, Smith JW, Garrison RN, Downard CD. Intraperitoneal 1.5% Delflex improves intestinal blood flow in necrotizing enterocolitis. J Surg Res. 2013; 184:358-64.
[63] Lu XG, Kang X, Zhou FQ, et al. Effects of pyruvate-enriched peritoneal dialysis solution on intestinal barrier in peritoneal resuscitation from hemorrhagic shock in rats. J Surg Res. 2015; 193:368-76.
[64] Algieri F, Rodriguez-Nogales A, Garrido-Mesa J, et al. Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate. Biochem Pharmacol. 2016; 103:53-63.
[65] Marques NR, Baker RD, Kinsky N, et al. Effectiveness of colonic fluid resuscitation in a burn-injured swine. J Burn Care Res. 2018; 39:744-50.
[66] Ziolkowski W, Wierzba TH, Kaczor JJ, et al. Intravenous sodium pyruvate protects against cerulein-induced acute pancreatitis. Pancreas. 2008; 37:238-9.
[67] 钱远宇,张学金,刘杰,王鑫鑫,孟庆义.饮用口服补液盐和苏打水预防横纹肌溶解症的效果研究[J].河北医学. (with English abstract) 2011; 17:1581-4.
[68] Olek RA, Antosiewicz J, Popinigis J, Gabbianelli R, Fedeli D, Falcioni G. Pyruvate but not lactate prevents NADH-induced myoglobin oxidation. Free Radic Biol Med. 2005; 38:1484-90.
[69] Kooiman J, de Vries JPM, Van der Heyden J, et al. Randomized trial of one-hour sodium bicarbonate vs standard periprocedural saline hydration in chronic kidney disease patients undergoing cardiovascular contrast procedures. PLoS One. 2018; 13:e0189372.
[70] Zilberter Y, Gubkina O, Ivanov AI. A unique array of neuroprotective effects of pyruvate in neuropathology. Front Neurosci. 2015; 9:17.
[71] Mungo E, Bergandi L, Salaroglio IC, Doublier S. Pyruvate treatment restores the effectiveness of chemotherapeutic agents in human colon adenocarcinoma and pleural mesothelioma cells.
[72] Wojtkowiak JW, Cornnell HC, Matsumoto S, et al. Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302. Cancer Metab. 2015; 3(1):2.
[73] Van Erven PM, Gabreëls FJ, Wevers RA, et al. Intravenous pyruvate loading test in Leigh syndrome. J Neurol Sci. 1987; 77:217-27.
[74] Zhou FQ. Stable aqueous solution containing sodium pyruvate and the preparation and use thereof. US Patent issued. US 8, 835, 508 B2, 2014.
[75] Zhou FQ. Pyruvate is superior to chloride in hypertonic saline in resuscitation. Shock. 2008; 30:610-1.
[76] 周方强.丙酮酸钠的治疗作用和液体治疗溶液改进的探讨[D].全国新药研发与技术审评及注册管理研讨会论文集. 2010; p.133-43, 成都.
[77] 周方强,刘锐.丙酮酸钠在危重病液体治疗中的潜在应用[J].中华损伤与修复杂志. (电子版,with English abstract) 2017; 12:321-5。
[78] Hu S, Dai YL, Gao MJ, et al. Pyruvate as a novel carrier of hydroxyethyl starch 130/0.4 may protect kidney in rats subjected to severe burns. J Surg Res. 2018; 225:166-74.
[79] 韩晓春,胡森,刘先奇,方涛,白晓东.丙酮酸钠液对烫伤休克大鼠肾血管通透性的影响[J].中国医学工程.(with English abstract) 2011; 19:1-6。
[80] Patiño AM, Marsh RH, Nilles EJ, Baugh CW, Rouhani SA, Kayden S. Facing the shortage of IV fluids - A hospital-based oral rehydration strategy. New Engl J Med. 2018; 378:1475-7.
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  • @article{10034930,
      author = {Zhou Fangqiang},
      title = {Pyruvate Application Indicates an Important Medical Advance},
      journal = {Asia-Pacific Journal of Medicine},
      volume = {1},
      number = {1},
      pages = {14-20},
      url = {https://www.sciencepublishinggroup.com/article/10034930},
      abstract = {On the occasion of the 50th anniversary of WHO-guided oral rehydration salts (ORS) clinical application, this review mainly discussed recent findings in ORS, a novel pyruvate-enriched ORS (Pyr-ORS), in animal experiments. Since past several decades, numerous pieces of evidence have shown that pyruvate owns superior biological and pharmacological characteristics that benefit critical care patients: enhancement of anoxia/hypoxia tolerance, correction of hypoxic lactic acidosis, antagonism of oxidative stress and inflammation, protection of mitochondrial structure and function and anti-apoptosis, etc. Therefore, pyruvate prevents from multi-organ dysfunction and corrects disturbances of glucose metabolism and acid-base balance in patients subjected with various pathogen insults. In recent years, investigations of intravenous pyruvate and oral pyruvate in ORS demonstrated properties above and a double increase of survival in animals subjected to hemorrhagic or burn shock. In the review, biological properties of pyruvate and the high efficiency, underlying mechanisms and vast potential clinical indications of Pyr-ORS were illustrated. The review points out that pyruvate-enriched fluids may be the third generation of fluid therapy, not only a volume expander, but also a therapeutic agent for organ dysfunction and metabolic disturbance; pyruvate may be the first-line drug for fluid therapy: Pyr-ORS becomes the first choice for patients who require fluid rehydration alone or in combination with intravenous pyruvate. Pyruvate applications would improve overall clinical outcomes of various diseases, particularly critical illnesses, potentiating a new most important medical advance this century.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - Pyruvate Application Indicates an Important Medical Advance
    AU  - Zhou Fangqiang
    Y1  - 2019/01/04
    PY  - 2019
    T2  - Asia-Pacific Journal of Medicine
    JF  - Asia-Pacific Journal of Medicine
    JO  - Asia-Pacific Journal of Medicine
    SP  - 14
    EP  - 20
    PB  - Science Publishing Group
    UR  - http://www.sciencepg.com/article/10034930
    AB  - On the occasion of the 50th anniversary of WHO-guided oral rehydration salts (ORS) clinical application, this review mainly discussed recent findings in ORS, a novel pyruvate-enriched ORS (Pyr-ORS), in animal experiments. Since past several decades, numerous pieces of evidence have shown that pyruvate owns superior biological and pharmacological characteristics that benefit critical care patients: enhancement of anoxia/hypoxia tolerance, correction of hypoxic lactic acidosis, antagonism of oxidative stress and inflammation, protection of mitochondrial structure and function and anti-apoptosis, etc. Therefore, pyruvate prevents from multi-organ dysfunction and corrects disturbances of glucose metabolism and acid-base balance in patients subjected with various pathogen insults. In recent years, investigations of intravenous pyruvate and oral pyruvate in ORS demonstrated properties above and a double increase of survival in animals subjected to hemorrhagic or burn shock. In the review, biological properties of pyruvate and the high efficiency, underlying mechanisms and vast potential clinical indications of Pyr-ORS were illustrated. The review points out that pyruvate-enriched fluids may be the third generation of fluid therapy, not only a volume expander, but also a therapeutic agent for organ dysfunction and metabolic disturbance; pyruvate may be the first-line drug for fluid therapy: Pyr-ORS becomes the first choice for patients who require fluid rehydration alone or in combination with intravenous pyruvate. Pyruvate applications would improve overall clinical outcomes of various diseases, particularly critical illnesses, potentiating a new most important medical advance this century.
    VL  - 1
    IS  - 1
    ER  - 

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  • Dialysis Centers, Fresenius Medical Care, Chicago, USA

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