Prophylactic effect of ethyl pyruvate on renal ischemia/reperfusion injury mediated through oxidative stress

Bloom, Jonathan; Patel, Neel; Wagmaister, Jonathan; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

doi:10.1007/s11255-018-2020-9

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…It seems that the effect of EP was mediated through enhanced expression of glycolytic enzymes, HK2 and GAPDH. Similar effects of EP were observed in renal tubular endothelial cells where EP prevented hydrogen peroxide-induced reduction of hexokinase activity and ATP [24].…”

Section: Discussionsupporting

confidence: 70%

Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis

et al. 2020

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Ethyl pyruvate (EP), a stable form of pyruvate, has shown beneficial effects in animal models of shock, ischemia/reperfusion injury, and sepsis due to its potent anti-oxidant and anti-inflammatory properties. Our recent study demonstrated that EP application prevented the clinical manifestation of type 1 diabetes in mice by augmenting regulatory T cell (Treg) number and function. Our present study shows that EP increases Treg proliferation and suppressive function (perforin and IL-10 expression) during in vitro differentiation from conventional CD4+CD25− T cells. Enhanced expansion of Treg after EP treatment correlated with increased ATP levels and relied on increased glycolysis. Inhibition of oxidative phosphorylation did not attenuate EP stimulatory effects, suggesting that this metabolic pathway was not mandatory for EP-driven Treg proliferation. Moreover, EP lowered the expression of carnitine palmitoyltransferase I, an enzyme involved in fatty acid oxidation. Further, the stimulatory effect of EP on Treg proliferation was not mediated through inhibition of the mTOR signaling pathway. When given in vivo either intraperitoneally or orally to healthy C57BL/6 mice, EP increased the number of Treg within the peritoneal cavity or gut-associated lymphoid tissue, respectively. In conclusion, EP promotes in vitro Treg proliferation through increased glycolysis and enhances Treg proliferation when administered in vivo.

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Section: Discussionsupporting

confidence: 70%

Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis

et al. 2020

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“…However, with a higher concentration of glucose in the substrate the brain slices were exposed to, EP contribution to energy metabolism was not overly significant, if not redundant [ 30 ]. Still, EP also prevented hydrogen peroxide-induced reduction of ATP and hexokinase (a glycolytic enzyme) activity in renal tubular endothelial cells [ 31 ]. Excessive ROS can impair mitochondria by inducing mutations in mitochondrial DNA or damaging the mitochondrial respiratory chain [ 32 ], which can lead to dysfunctional oxidative phosphorylation.…”

Section: Ethyl Pyruvate a Jack Of All Tradesmentioning

confidence: 99%

Ethyl pyruvate, a versatile protector in inflammation and autoimmunity

et al. 2022

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Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years.

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“…generation of reactive oxygen species (ROS), 5 so that certain antioxidants could effectively abolish OXS. In fact, our early study 6 showed that ethyl pyruvate (EPy), a potent antioxidant, counteracted with H 2 O 2 , a typical OXS inducer, to protect MDCK renal cells from renal cell injury in vitro. Although H 2 O 2 led to a drastic 90% reduction in MDCK cell viability (only 10% viable), EPy was capable of maintaining >90% cell viability under such H 2 O 2 -exerted OXS [Figure 1(A)].…”

Section: Introductionmentioning

confidence: 99%

Prophylactic effect of ethyl pyruvate on renal ischemia/reperfusion injury in rats

Yau¹,

Bloom²,

Wagmaister³

et al. 2021

UNOAJ

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Background: Following our hypothesis that oxidative stress might play a primary role in renal ischemia/reperfusion injury (RIRI), we investigated if ethyl pyruvate (EPy) with potent antioxidant activity might prevent or alleviate RIRI induced in rats. Methods: Sprague-Dawley rats were randomly divided into four groups: (A) Sham, (B) renal ischemia/reperfusion (RIR), (C) RIR with EPy supplement (RIR+EPy), and (D) RIR with Mann supplement (RIR+Mann). Mannitol (Mann), a preoperative agent being clinically used, was tested for comparison with EPy. Rats were subjected to 40-min ischemia, followed by 24-h reperfusion. Either EPy or Mann was given to rats 30 min prior to ischemia and immediately before the reperfusion period. Results: The RIR and RIR+Mann groups showed palpable kidney injuries with the ~5-fold elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, indicating renal dysfunction. However, the kidneys in the RIR+EPy group appeared merely normal (similar to the Sham’s) with the basal BUN/Cr levels, indicating normal renal function. No effects on histology, BUN or Cr were yet seen with Mann. Moreover, specific kidney injury markers were up-regulated and oxidative stress was also ~2.1-fold severer in the RIR group, whereas little changes in those markers and oxidative stress were seen with EPy supplement (RIR+EPy). Conclusions: Although oxidative stress feasibly plays a key role in RIRI, EPy with antioxidant activity is capable of protecting the kidneys from such an assault. Thus, EPy (not Mann) should be considered as an effective perioperative renoprotective agent that could be used clinically.

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Prophylactic effect of ethyl pyruvate on renal ischemia/reperfusion injury mediated through oxidative stress

Cited by 3 publications

References 36 publications

Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis

Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis

Ethyl pyruvate, a versatile protector in inflammation and autoimmunity

Prophylactic effect of ethyl pyruvate on renal ischemia/reperfusion injury in rats

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