Pyruvate is a three-carbon ketoacid that occurs naturally in cells. It is produced through enzymatic reactions in the glycolytic pathway and plays a crucial role in energy metabolism. Despite promising early results, later well-controlled studies of physically active people have shown that pyruvate supplementation lasting more than 1 week has no ergogenic effects. However, some data suggest that ingested pyruvate may be preferentially metabolized without accumulation in the bloodstream. Pyruvate exhibits antioxidant activity and can affect the cellular redox state, and exogenous pyruvate can influence metabolism by affecting the acid-base balance of the blood. This brief review focuses on the potential effects of pyruvate as a supplement for active people. The current state of understanding suggests that studies of the effects of pyruvate supplementation should prioritize investigating the timing of pyruvate intake.

2024-11-01·Angiogenesis

Mitochondrial control of hypoxia-induced pathological retinal angiogenesis

Article

作者: Yagi, Hitomi ; Lee, Jeff ; Negishi, Kazuno ; Zeng, Yan ; Fu, Zhongjie ; Wang, Chaomei ; Nian, Shen ; Smith, Lois E H ; Kasai, Taku ; Singh, Sasha A ; Aikawa, Masanori ; Neilsen, Katherine ; Boeck, Myriam ; Hellström, Ann ; Grumbine, Matthew ; Sweet, Ian R

AbstractObjectivePathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization.MethodsOIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation.ResultsIn OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV.ConclusionsMitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases.

2024-10-01·The Journal of Heart and Lung Transplantation

A novel cardioprotective perfusion protocol prevents functional decline during extended normothermic ex situ heart perfusion of porcine hearts

Article

作者: Kaffka Genaamd Dengler, Selma E ; Doevendans, Pieter A ; Ballan, Elisa M. ; Vervoorn, Mats T. ; Kaffka genaamd Dengler, Selma E. ; Vervoorn, Mats T ; Ballan, Elisa M ; Sluijter, Joost P G ; van Tuijl, Sjoerd ; van der Kaaij, Niels P ; de Jager, Saskia C.A. ; Doevendans, Pieter A. ; Sluijter, Joost P.G. ; de Jager, Saskia C A ; van der Kaaij, Niels P.

INTRODUCTIONA common limitation to normothermic ex situ heart perfusion (ESHP) is functional decline. We previously designed a cardioprotective normothermic perfusion protocol, incorporating adenosine-lidocaine cardioplegia, subnormothermic reperfusion, pyruvate and methylprednisolone supplementation, and hemofiltration to prevent myocardial functional decline over 4 hours. In this study, we added continuous catecholamine infusion and protective loading conditions to assess the effectiveness of this enhanced cardioprotective perfusion protocol in preventing functional decline during extended normothermic perfusion in marginal porcine hearts.MATERIALS & METHODSSix slaughterhouse pig hearts underwent 9 hours of normothermic ESHP using the enhanced cardioprotective protocol. Cardiac function was assessed at 90, 120, 240, 360, 480 and 540 minutes of ESHP. Subsequently, a preload-challenge was conducted after 9 hours to assess preload-responsiveness (mimicking the Frank-Starling principle) and suitability for transplantation.RESULTSDuring perfusion, myocardial function remained stable, indicated by consistent mean cardiac index (9.2 L/min/kg at 90; 9.3 L/min/kg at 540 minutes of ESHP), left ventricular stroke work index (6258 mmHg*ml/kg at 90; 6707 mmHg*ml/kg at 540 minutes) and rate of ventricular pressure change over time. In response to a preload-challenge, there was a notable increase of 34% in mean cardiac index and 58% in mean stroke work.CONCLUSIONOur study demonstrates that the implementation of a cardioprotective protocol enables (very) marginal porcine slaughterhouse hearts, subjected to both a warm and cold ischemic insult prior to ESHP, to sustain satisfactory cardiac function without notable decline during 9 hours of normothermic ESHP, while also preserving their preload-responsiveness. The latter finding might indicate suitability for transplantation. This study provides a groundwork for further extending normothermic ESHP, unlocking the full potential of this promising technology.

100 项与 Pyruvate 相关的药物交易

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