Abstract
BackgroundWe hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects.MethodsRat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR), with or without GPC administration. The reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed.ResultsGPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers.ConclusionGPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes.
Highlights
Ischemia-reperfusion (IR) injury is a common complication of inflow-controlled major surgical resections and organ transplantations
In vitro experiments were conducted in order to analyse the dose-response effects of GPC on the respiratory activity of rat liver mitochondria in normoxia or anoxicconditions
The electron transport chain (ETC) and oxidative phosphorylation (OxPhos) capacity of mitochondria was influenced significantly when GPC was applied at 200 mM concentration (Fig 1B)
Summary
Ischemia-reperfusion (IR) injury is a common complication of inflow-controlled major surgical resections and organ transplantations. The prolonged lack of oxygen during ischemia is accompanied by an inevitable decrease in ATP production and an increase in ATP hydrolysis, while the overproduction of reactive oxygen and nitrogen species (ROS and RNS, respectively) during the reoxygenation phase leads to oxidative and nitrosative stress and membrane function failure. In addition to these events, the IR-induced increased activity of the main lipolytic enzymes results in modified biomembrane structures, leading to a loss of essential membrane-forming glycerophospholipids[1, 2]. We hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects
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