Diabetes is prevalent worldwide, but ideally intensive therapeutic strategy in clinical diabetes and diabetic nephropathy (DN) is still lack. Pyruvate is protective from glucometabolic disturbances and kidney dysfunction in various pathogenic insults. Present studies focused on oral pyruvate effects on diabetes status and DN with 0.35% pyruvate in pyruvate-enriched oral rehydration solution (Pyr-ORS) and 1% pyruvate as drinking water for 8 weeks, using the model of diabetic db/db mice. Both Pyr-ORS and 1% pyruvate showed comparable therapeutic effectiveness with controls of body weight and blood sugar, increases of blood insulin levels, and improvement of renal function and pathological changes. Aberrant key enzyme activities in glucometabolic pathways, AR, PK, and PDK/PDH, were also restored; indexes of oxidative stress and inflammation, NAD+/NADH ratio, and AGEs in the kidneys were mostly significantly preserved after pyruvate treatments. We concluded that oral pyruvate delayed DN progression in db/db mice and the modified Pyr-ORS formula might be an ideal novel therapeutic drink in clinical prevention and treatment of type 2 diabetes and DN.

Pyr-ORS provides a superior option to Cit-ORS for the preservation of intestinal blood flow and barrier function and the attenuation of histopathological alterations in enteral resuscitation of rats with burn injury. Its underlying mechanism may be closely related to the pyruvate in activation of intestinal HIF-1-EPO signaling cascades.

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Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase (PDH) activator with several unique beneficial biological properties, including anti-oxidant and anti-inflammatory effects and the ability to activate the hypoxia-inducible factor-1 (HIF-1α) - erythropoietin (EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.

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Pyruvate was advantageous over citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to lethal burn shock in 24 h.

To investigate the effects of pyruvate (Pyr) on adenosine triphosphate (ATP), endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) in red blood cells (RBCs) during the cardiopulmonary bypass procedure (CPB), blood, 500 mL, was collected from each of 10 healthy dogs (weight 12–18 kg). The blood was divided into two parts (250 mL each) and randomly assigned into the control group (Group C, n = 10) or the Pyr group (Group P, n = 10). The blood was commingled with an equal volume of 0.9% NaCl and pyruvated isotonic solution (Pyr 50 mM) in the extracorporeal circuit in the two groups, respectively. The CPB procedure was fixed at 120 min, and the transferring flow was 4 L/min. Contents of ATP in RBCs, eNOS activities, and NO productions in plasma were measured before CPB and during CPB at 30, 60, 90, and 120 min in both groups. The ATP level, eNOS activity, and NO production were not different prior to CPB between the two groups. A decline of ATP levels was shown in both groups but remained significantly higher in Group P than in Group C at the same time points during in vitro CPB (P < 0.01). Values of eNOS and NO were significantly increased in Group C but markedly reduced in Group P during CPB, compared with pre‐CPB (P < 0.01). The CPB procedure significantly damaged dogs’ RBCs in the ATP level, eNOS activity, and NO production, in vitro, but Pyr effectively protected RBCs in these functions during CPB. Pyr would be clinically protective for RBCs during CPB.