Bench-to-bedside review: Amelioration of acute renal impairment using ethyl pyruvate

Michael C Reade,Mitchell P Fink

doi:10.1186/cc3892

Michael C Reade, Mitchell P Fink

Open Access

https://doi.org/10.1186/cc3892

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Abstract

Inflammation and oxidative stress cause renal impairment. Renal failure exacerbates the effect of oxidative stress on many organ systems. Antioxidants can prevent or treat renal failure in various experimental models and clinical situations. Pyruvate is an endogenous antioxidant with beneficial effects in animal models of oxidative stress. Because sodium pyruvate rapidly degrades in solution, a simple derivative of pyruvic acid, namely ethyl pyruvate, has been investigated as a therapeutic agent in preclinical studies. Ethyl pyruvate reduces organ system damage in ischaemia/reperfusion injury and haemorrhagic and endotoxic shock, at least in part through its antioxidant action. In addition, ethyl pyruvate appears to have direct beneficial effects on cytokine expression and proinflammatory gene regulation. The effect is long lasting and, importantly, even when it is administered after the onset of inflammation it can ameliorate organ damage and improve survival. Ethyl pyruvate is a widely used as a food additive and was shown to be safe in phase I clinical trials. We suggest ethyl pyruvate warrants further evaluation in the management of acute renal impairment.

Highlights

Acute renal failure is associated with oxidative stress [1]
Treatment with ethyl pyruvate was more effective than sodium pyruvate in preventing the proinflammatory cytokine stimulated hyperpermeability and induction of inducible nitric oxide synthase in Caco-2 human enterocyte-like monolayers in vitro, and in protecting against ileal mucosal hyperpermeability, bacterial translocation and hepatocellular injury in mice given LPS in vivo [22]
It would seem from these animal and cellular models that ethyl pyruvate reduces oxidative stress and the damage done by oxygen free radicals in a variety of tissues

Summary

Introduction

Acute renal failure is associated with oxidative stress [1]. This relationship appears to be both cause and effect because dialysis reduces markers of oxidative stress in patients with acute renal failure [2] and various antioxidants are able to ameliorate experimental renal injury [3,4]. In a mouse model of resuscitated haemorrhagic shock [17] ethyl pyruvate improved survival at 24 hours, reduced bacterial translocation to mesenteric lymph nodes, and prevented the development of increased ileal mucosal permeability It prolonged survival time and was associated with significantly lower circulating concentrations of nitrite/nitrate and IL-6 and higher plasma levels of IL-10 in a rats given a bolus of lipopolysaccharide (LPS) [18]. Treatment with ethyl pyruvate was more effective than sodium pyruvate in preventing the proinflammatory cytokine stimulated hyperpermeability and induction of inducible nitric oxide synthase (iNOS) in Caco-2 human enterocyte-like monolayers in vitro, and in protecting against ileal mucosal hyperpermeability, bacterial translocation and hepatocellular injury in mice given LPS in vivo [22]. Since the Food and Drug Administration has permitted the company to carry out a phase II randomized controlled trial of ethyl pyruvate in high-risk patients undergoing cardiac surgery and cardiopulmonary bypass [35], major safety concerns apparently were not raised by the agency

Conclusion

12. Food and Agriculture Organization of the United Nations and the