Pyruvate in Potential Supportive Therapy in Critical Covid-19
DOI: 194 Downloads 4440 Views
Author(s)
Abstract
The focus of present review is on the proposal that pyruvate may be a potential candidate in treating critical care patients with Covid-19 virus infection. The pyruvate anion has beneficial properties to protect organ function by increase of hypoxia/anoxia tolerance, correction of hypoxic lactic acidosis, exertion of anti-oxidative stress/inflammation, protection of mitochondrial function and inhibition of apoptosis. The key effect is reactivation of depressed pyruvate dehydrogenase in various pathogenic insults. These benefits are unparalleled with anions in current medical fluids. Pyruvate in intravenous or oral rehydration salt (ORS) may be a powerful supportive care in treatment of severe virus infection with Covid-19 and critical care patients. Recent studies demonstrate that intravenous pyruvate is superior to regular fluids and pyruvate-enriched ORS (Pyr-ORS) is advantageous over WHO-ORS in organ protection, acidosis correction and survival improvement in severe shock resuscitation in animals. While pyruvate is not yet approved by the FDA, there were many clinical studies on treatment of various diseases with a large dosage of its intravenous or oral form since 1940s. These studies, using the products at the time, indicate pyruvate’s clinical effectiveness and absence of adverse effects, which resembled the phase II clinical trial of a novel drug. Therefore, it is logical to consider randomized clinical trials of pyruvate in treatment of Covid-19 or Ebola infection as well as critical care patients as a beneficial supportive therapy, albeit it is not an anti-virus agent, particularly using a low pyruvate dose in Pyr-ORS formulas, under protocols of compassionate use.
Keywords
Hypoxia, Lactic acidosis, Oral rehydration salt, Pyruvate, Resuscitation, Virus, Covid-19
Cite this paper
Zhou, Fang-Qiang,
Pyruvate in Potential Supportive Therapy in Critical Covid-19
, SCIREA Journal of Clinical Medicine.
Volume 5, Issue 3, June 2020 | PP. 50-65.
References
[ 1 ] | Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. doi: 10.1016/S0140-6736(20)30183-5. |
[ 2 ] | Fischer WA 2nd, Crozier I, Bausch DG, Muyembe JJ, Mulangu S, Diaz JV, Kojan R, Wohl DA, Jacob ST. Shifting the paradigm - applying universal standards of care to Ebola virus disease. N Engl J Med. 2019;380:1389-91. doi: 10.1056/NEJMp1817070. |
[ 3 ] | Ansumana R, Jacobsen KH, Sahr F, Idris M, Bangura H, Boie-Jalloh M, Lamin JM, Sesay S. Ebola in Freetown area, Sierra Leone--a case study of 581 patients. N Engl J Med. 2015;372:587-8. doi: 10.1056/NEJMc1413685. |
[ 4 ] | Mongan PD, Fontana JL, Chen R, Bünger R. Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. Am J Physiol. 1999;277:H2253-63. doi: 10.1152/ajpheart.1999.277.6.H2253. |
[ 5 ] | Flaherty DC, Hoxha B, Sun J, Gurji H, Simecka JW, Mallet RT, Olivencia-Yurvati AH.Pyruvate-fortified fluid resuscitation improves hemodynamic stability while suppressing systemic inflammation and myocardial oxidative stress after hemorrhagic shock. Mil Med. 2010;175:166-72. doi:10.7205/milmed-d-09-00161. |
[ 6 ] | Hu S, Bai XD, Liu XQ, Wang HB, Zhong YX, Fang T, Zhou FQ. Pyruvate Ringer's solution corrects lactic acidosis and prolongs survival during hemorrhagic shock in rats. J Emerg Med. 2013;45:885-93. doi: 10.1016/j.jemermed.2013.04.062. |
[ 7 ] | Hu S, Liu WW, Zhao Y, Lin ZL, Luo HM, Bai XD, Sheng ZY, Zhou FQ. Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns. Burns. 2014;40:693-701. doi: 10.1016/j.burns.2013.09.030. |
[ 8 ] | Yu W, Hu S, Xie ZY, He ZJ, Luo HM, Lin HY, Zhou FQ, Sheng ZY. Pyruvate oral rehydration solution improved visceral function and survival in shock rats. J Surg Res. 2015;193:344-54. doi: 10.1016/j.jss.2014.06.037. |
[ 9 ] | Liu R, Hu XH, Wang SM, Guo SJ, Li ZY, Bai XD, Zhou FQ, Hu S. Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs. Burns. 2016;42:797-806. doi: 10.1016/j.burns.2016.01.012. |
[ 10 ] | Zhou FQ. Pyruvate research and clinical application outlooks a revolutionary medical advance. Int J Nutr. 2020;5:1-8. doi: 10.14302/issn.2379-7835.ijn-20-3159. |
[ 11 ] | 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. doi: 10.1111/j.1525-1594.2012.01482.x. |
[ 12 ] | Acharya AP, Rafi M, Woods EC, Gardner AB, Murthy N. Metabolic engineering of lactate dehydrogenase rescues mice from acidosis. Sci Rep. 2014;4:5189. doi: 10.1038/srep05189. |
[ 13 ] | Sheeran FL, Angerosa J, Liaw NY, Cheung MM, Pepe S. Adaptations in protein expression and regulated activity of pyruvate dehydrogenase multienzyme complex in human systolic heart failure. Oxid Med Cell Longev. 2019 Feb 7;2019:4532592. doi: 10.1155/2019/4532592. |
[ 14 ] | Wu CY, Satapati S, Gui W, Wynn RM, Sharma G, Lou M, Qi X, Burgess SC, Malloy C, Khemtong C, Sherry AD, Chuang DT, Merritt ME. A novel inhibitor of pyruvate dehydrogenase kinase stimulates myocardial carbohydrate oxidation in diet-induced obesity. J Biol Chem. 2018;293:9604-13. doi: 10.1074/jbc.RA118.002838. |
[ 15 ] | Sato K, Mochida S, Tomimoto D, Konuma T, Kiyota N, Tsuda S, Shiga Y, Omodaka K, Nakazawa T. A pyruvate dehydrogenase kinase inhibitor prevents retinal cell death and improves energy metabolism in rat retinas after ischemia/reperfusion injury. Exp Eye Res. 2020;193:107997. doi: 10.1016/j.exer.2020.107997. |
[ 16 ] | Zhang XM, Wang YZ, Tong JD, Ning XC, Zhou FQ, Yang XH, Jin HM. Pyruvate alleviates high glucose-induced endoplasmic reticulum stress and apoptosis in HK-2 cells. FEBS Open Bio. 2020 Mar 9. doi: 10.1002/2211-5463.12834. |
[ 17 ] | 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. doi: 10.1186/s40779-018-0160-y. |
[ 18 ] | 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. doi: 10.1016/j.jss.2018.01.018. |
[ 19 ] | Koga Y, Povalko N, Katayama K, Kakimoto N, Matsuishi T, Naito E, Tanaka M. Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene. Brain and Development. 2012;34:87–91. doi:10.1016/j.braindev.2011.03.003. |
[ 20 ] | Wang F, Hou H, Luo Y, Tang G, Wu S, Huang M, Liu W, Zhu Y, Lin Q, Mao L, Fang M, Zhang H, Sun Z. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight. 2020 Apr 23. pii: 137799. doi: 10.1172/jci.insight.137799. |
[ 21 ] | Xia S, Chen G, Wang B, Yin Y, Sun Z, Zhao J, Li P, Zhao L, Zhou H. Addition of sodium pyruvate to stored red blood cells attenuates liver injury in a murine transfusion model. Mediators Inflamm. 2016;2016:3549207. https://doi.org/10.1155/2016/3549207. |
[ 22 ] | Liu R, Wang SM, Liu XQ, Guo SJ, Wang HB, Hu S, Zhou FQ, Sheng ZY. Erratum to "Pyruvate alleviates lipid peroxidation and multiple organ dysfunction in rats with hemorrhagic shock" (Am J Emerg Med 34[3]:525-530). Am J Emerg Med. 2016;34:1330. doi: 10.1016/j.ajem.2016.04.035. |
[ 23 ] | Zhang JJ, Deng JT, Shen HQ, Jiang LL, He QW, Zhan J, Zhang ZZ, Wang YL. Pyruvate protects against intestinal injury by inhibiting the JAK/STAT signaling pathway in rats with hemorrhagic shock. J Surg Res. 2020;248:98-108. doi: 10.1016/j.jss.2019.11.012. |
[ 24 ] | Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55:105954. doi: 10.1016/j.ijantimicag.2020.105954. |
[ 25 ] | Tanaka KI, Shimoda M, Kawahara M. Pyruvic acid prevents Cu2+/Zn2+-induced neurotoxicity by suppressing mitochondrial injury. Biochem Biophys Res Commun. 2018;495:1335-41. doi: 10.1016/j.bbrc.2017.11.152. |
[ 26 ] | Iannetti EF, Smeitink JAM, Willems PHGM, Beyrath J, Koopman WJH. Rescue from galactose-induced death of Leigh syndrome patient cells by pyruvate and NAD+. Cell Death Dis. 2018;9:1135. doi: 10.1038/s41419-018-1179-4. |
[ 27 ] | Hu S, Dai YL, Gao MJ, Wang XN, Wang HB, Dou YQ, Bai XD, Zhou FQ. 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. doi: 10.1016/j.jss.2018.01.003. |
[ 28 ] | Mallet RT, Olivencia-Yurvati AH, Bünger R. Pyruvate-enriched resuscitation for shock. Exp Biol Med (Maywood). 2018;243:663-4. doi: 10.1177/1535370218773717. |
[ 29 ] | Hamburger T, Broecker-Preuss M, Hartmann M, Schade FU, de Groot H, Petrat F. Effects of glycine, pyruvate, resveratrol, and nitrite on tissue injury and cytokine response in endotoxemic rats. J Surg Res. 2013;183:e7-21. doi: 10.1016/j.jss.2013.01.024. |
[ 30 ] | McCall CE, Zabalawi M, Liu T, Martin A, Long DL, Buechler NL, Arts RJW, Netea M, Yoza BK, Stacpoole PW, Vachharajani V. Pyruvate dehydrogenase complex stimulation promotes immunometabolic homeostasis and sepsis survival. JCI Insight. 2018;3. pii: 99292. doi: 10.1172/jci.insight.99292. |
[ 31 ] | Bueding E, Goldfarb W. Blood changes following glucose, lactate and pyruvate injections in man. J Biol Chem 1943;147:33-40. |
[ 32 ] | Mateva L, Petkova I, Petrov K, Beniozef D, Bojilova M, Vankova L, Thorn W. Ten-Day course of sodium pyruvate infusions in patients with chronic liver diseases (CLD). Jpn Pharmacol Ther 1996;24:2629-39. |
[ 33 ] | Petkova I, Mateva L, Petrov K, Beniozef D, Thorn W. Effects of sodium pyruvate applied in patients with chronic liver diseases (CLD) of different etiology. Comptes rendus de l’Acad´emie bulgare des Sciences: Medecine Clinique 2003;56:107-12. |
[ 34 ] | Hermann HP, Pieske B, Schwarzmuller E, Keul J, Just H, Hasenfuss G. Haemodynamic effects of intracoronary pyruvate in patients with congestive heart failure: an open study. Lancet 1999;353:1321-3. doi:10.1016/s0140-6736(98)06423-x. |
[ 35 ] | 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. doi: 10.1007/s00392-010-0261-4. |
[ 36 ] | Olivencia-Yurvati AH, Blair JL, Baig M, Mallet RT. Pyruvate-enhanced cardioprotection during surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2003;17:715-20. doi:10.1053/j.jvca.2003.09.007. |
[ 37 ] | Sheeran FL, Angerosa J, Liaw NY, Cheung MM, Pepe S. Adaptations in protein expression and regulated activity of pyruvate dehydrogenase multienzyme complex in human systolic heart failure. Oxid Med Cell Longev. 2019;2019:4532592. doi: 10.1155/2019/4532592. |
[ 38 ] | Van Erven PM, Gabreëls FJ, Wevers RA, Doesburg WH, Ruitenbeek W, Renier WO, Lamers KJ. Intravenous pyruvate loading test in Leigh syndrome. J Neurol Sci. 1987;77:217-27. doi:10.1016/0022-510x(87)90124-9. |
[ 39 ] | ++Petkova I, Hristov V, Petrov K, Thorn W. Oral application of sodium pyruvate in healthy persons and patients with diabetes mellitus type 1. Comptes rendus de l’Acad´emie bulgare des Sciences: Medecine Clinique. 2007;60:579-84. |
[ 40 ] | Inoue T, Murakami N, Ayabe T, Oto Y, Nishino I, Goto Y, Koga Y, Sakuta R. Pyruvate improved insulin secretion status in a mitochondrial diabetes mellitus patient. J Clin Endocrinol Metab. 2016;101:1924-6. doi: 10.1210/jc.2015-4293. |
[ 41 ] | Nagasaka H, Komatsu H, Inui A, Nakacho M, Morioka I, Tsukahara H, Kaji S, Hirayama S, Miida T, Kondou H, Ihara K, Yagi M, Kizaki Z, Bessho K, Kodama T, Iijima K, Saheki T, Yorifuji T, Honda A. Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment. Mol Genet Metab. 2017;120:207-12. doi: 10.1016/j.ymgme.2016.12.011. |
[ 42 ] | Saito K, Kimura N, Oda N, Shimomura H, Kumada T, Miyajima T, Murayama K, Tanaka M, Fujii T. Pyruvate therapy for mitochondrial DNA depletion syndrome. Biochim Biophys Acta. 2012;1820:632-6. doi: 10.1016/j.bbagen.2011.08.006. |
[ 43 ] | Koga Y, Povalko N, Inoue E, Nashiki K, Tanaka M. Biomarkers and clinical rating scales for sodium pyruvate therapy in patients with mitochondrial disease. Mitochondrion. 2019;48:11-5. doi: 10.1016/j.mito.2019.02.001. |
[ 44 ] | Matthys D, Van Coster R, Verhaaren H. Fatal outcome of pyruvate loading test in child with restrictive cardiomyopathy. Lancet. 1991;338:1020-1. doi:10.1016/0140-6736(91)91884-w. |
[ 45 ] | Wu XQ, Li ZB, Chen WX, Wen DL, Zhang ZH, Xiong XM. The influence of different resuscitation solution on lactic acid accumulation after hemorrhagic shock: a network meta-analysis. Eur Rev Med Pharmacol Sci. 2019;23:6707-17. doi:10.26355/eurrev_201908_18562. |
[ 46 ] | McCague A, Bowman N, Wong DT. Lactic acidosis after resuscitation with sodium acetate. J Surg Res. 2012;173:362-4. doi: 10.1016/j.jss.2010.10.028. |
[ 47 ] | Webster KA. Hypoxia: life on the edge. Antioxid Redox Signal 2007;9:1303-7. doi:10.1089/ars.2007.1730. |
[ 48 ] | Minko T, Wang Y, Pozharov V. Remediation of cellular hypoxic damage by pharmacological agents. Curr Pharm Des 2005;11:3185-99. doi:10.2174/1381612054864948. |
[ 49 ] | Milner SM, Greenough WB 3rd, Asuku ME, Feldman M, Makam R, Noppenberger D, Price LA, Prosciak M, van Loon IN. From cholera to burns: a role for oral rehydration therapy. J Health Popul Nutr 2011;29:648-51. doi: 10.3329/jhpn.v29i6.9902. |
[ 50 ] | Patiño AM, Marsh RH, Nilles EJ, Baugh CW, Rouhani SA, Kayden S. Facing the shortage of IV fluids - A hospital-based oral rehydration strategy. N Engl J Med 2018;378:1475-7. doi: 10.1056/NEJMp1801772. |