Succinate salts in solving the «oxygen paradox» of reperfusion

Abstract

Reperfusion damage to the cellular structures of tissues in the early post-ischemic period is a consequence of the restoration of blood flow and reoxygenation. Currently, there is no effective treatment for reperfusion metabolic disorders in clinical practice. Over the past decades, biological studies of hypoxia and the role of hypoxia-inducible factor-1α (HIF-1), potentiating succinatoxidase oxidation by signal from the succinate-dependent receptor (GPR91), have significantly improved the understanding of oxygen homeostasis during the period of recovery of blood flow. HIF-1 plays a key role in postischemic damage and is an oxygen-sensitive transcription factor that mediates adaptive metabolic responses to hypoxia and hyperoxia during reperfusion and reoxygenation. Activation of HIF-1 by succinate improves cell survival in hypoxic and posthypoxic (hyperoxygenated) environment, altering energy metabolism, proliferation, angiogenesis and vascular remodeling. The role of succinate oxidation in the period of ischemia / reperfusion and reoxygenation suggests the widespread use of infusion succinate as a protector that reduces the degree of tissue damage by reactive oxygen species (ROS) and restores the usual oxygen homeostasis.