Ethyl Pyruvate as a Potential Defense Intervention against Cytokine Storm in COVID-19?

Tanwar, Omprakash; Soni, Aastha; Prajapat, Pawan; Shivhare, Tanu; Pandey, Pooja; Samaiya, Puneet Kumar; Pandey, Sharad Prakash; Kar, Parimal

doi:10.1021/acsomega.1c00157

Cited by 6 publications

(3 citation statements)

References 59 publications

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“…This uncontrolled systemic inflammatory response causes immunopathological events, leading to severe pneumonia, ARDS, multiple organ failure, and ultimately the death of a patient with COVID-19 [36,37]. To avoid such a scenario, it is necessary to monitor the expression of proinflammatory mediators from the onset of infection and, accordingly, to search for alternative treatment strategies during the period when the human body still has enough time to regulate its immunity to fight the infection [38].…”

Section: Discussionmentioning

confidence: 99%

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Grigorov,

Pejić,

Todorović

et al. 2023

IJMS

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The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

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Section: Discussionmentioning

confidence: 99%

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Grigorov,

Pejić,

Todorović

et al. 2023

IJMS

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“…Thus, pyruvate-enriched fluids would be an optimal selection to prevent postoperative hyperglycemia, probably due to its preservation of PDH and islet function (30)(31)(32)(33)60). At present, if pyruvate solutions were compassionately used in severe COVID-19 patients, clinical outcomes might have greatly improved (86,87). In the future, pyruvate-enriched fluids may encompass other medical solutions specifically used for RBC storage, cell salvage, organ preservation, cardioplegia, peritoneal dialysis, priming fluid for cardiopulmonary bypass circuits, and others (24,27,77,80,88).…”

Section: Pyruvate Saline Superior To Normal Salinementioning

confidence: 99%

Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids

Zhou

2022

Front. Med.

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There have been ongoing debates about resuscitation fluids because each of the current fluids has its own disadvantages. The debates essentially reflect an embarrassing clinical status quo that all fluids are not quite ideal in most clinical settings. Therefore, a novel fluid that overcomes the limitations of most fluids is necessary for most patients, particularly diabetic and older patients. Pyruvate is a natural potent antioxidant/nitrosative and anti-inflammatory agent. Exogenous pyruvate as an alkalizer can increase cellular hypoxia and anoxia tolerance with the preservation of classic glycolytic pathways and the reactivation of pyruvate dehydrogenase activity to promote oxidative metabolism and reverse the Warburg effect, robustly preventing and treating hypoxic lactic acidosis, which is one of the fatal complications in critically ill patients. In animal studies and clinical reports, pyruvate has been shown to play a protective role in multi-organ functions, especially the heart, brain, kidney, and intestine, demonstrating a great potential to improve patient survival. Pyruvate-enriched fluids including crystalloids and colloids and oral rehydration solution (ORS) may be ideal due to the unique beneficial properties of pyruvate relative to anions in contemporary existing fluids, such as acetate, bicarbonate, chloride, citrate, lactate, and even malate. Preclinical studies have demonstrated that pyruvate-enriched saline is superior to 0.9% sodium chloride. Moreover, pyruvate-enriched Ringer’s solution is advantageous over lactated Ringer’s solution. Furthermore, pyruvate as a carrier in colloids, such as hydroxyethyl starch 130/0.4, is more beneficial than its commercial counterparts. Similarly, pyruvate-enriched ORS is more favorable than WHO-ORS in organ protection and shock resuscitation. It is critical that attention first be paid to improving abnormal saline with pyruvate for ICU patients. Many clinical trials with a high dose of intravenous or oral pyruvate were conducted over the past half century, and results indicated its effectiveness and safety in humans. The long-term instability of pyruvate aqueous solutions and para-pyruvate cytotoxicity is not a barrier to the pharmaceutical manufacturing of pyruvate-enriched fluids for ICU patients. Clinical trials with sodium pyruvate-enriched solutions are urgently warranted.

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“… 76 It was newly further demonstrated that EP with glycyrrhizic acid through the inhibition of HMGB1 release and inflammatory senescence prevented Tau oligomers-induced cellular senescence and tauopathies, such as Alzheimer’s disease, in the brain of mice. 77 In this regard, EP was recently proposed in Covid-19 treatments, 78 as mentioned above due to susceptibility of cellular senescence to viral infection. 37 Similarly, pyruvate is also brain protective against tauopathy and sodium pyruvate was hypothesized in the intervention of Covid-19 viral infection, too.…”

Section: Pyruvate In Healthy Agingmentioning

confidence: 99%

NAD⁺, Senolytics, or Pyruvate for Healthy Aging?

Zhou

2021

Nutr Metab Insights

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In last decades, healthy aging has become one of research hotspots in life science. It is well known that the nicotinamide adenine dinucleotide oxidized form (NAD+) level in cells decreases with aging and aging-related diseases. Several years ago, one of NAD+ precursors was first demonstrated with its new role in DNA damage repairing in mice, restoring old mice to their physical state at young ones. The finding encourages extensive studies in animal models and patients. NAD+ and its precursors have been popular products in nutrition markets. Alternatively, it was also evidenced that clearance of cellular senescence by senolytics preserved multiorgan (kidney and heart) function and extended healthy lifespan in mice. Subsequent studies confirmed findings in elderly patients subjected with idiopathic pulmonary fibrosis. The senolytic therapy is now focused on various diseases in animal and clinical studies. However, pyruvate, as both a NAD+ substitute and a new senolytic, may be advantageous, on the equimolar basis, over current products above in preventing and treating diseases and aging. Pyruvate-enriched fluids, particularly pyruvate oral rehydration salt, may be a novel intervention for diseases and aging besides critical care. Albeit the direct evidence that benefits healthy aging is still limited to date, pyruvate, as both NAD+ provider and senolytic agent, warrants intensive research to compare NAD+ or senolytics for healthy aging, specifically on the equimolar basis, in effective blood levels. This review briefly discussed the recognition of healthy aging by comparing NAD+ and Senolytics with sodium pyruvate from the clinical point of view.

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Ethyl Pyruvate as a Potential Defense Intervention against Cytokine Storm in COVID-19?

Cited by 6 publications

References 59 publications

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids

NAD⁺, Senolytics, or Pyruvate for Healthy Aging?

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Ethyl Pyruvate as a Potential Defense Intervention against Cytokine Storm in COVID-19?

Cited by 6 publications

References 59 publications

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids

NAD+, Senolytics, or Pyruvate for Healthy Aging?

Contact Info

Product

Resources

About

NAD⁺, Senolytics, or Pyruvate for Healthy Aging?