Abstract
Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action.
Highlights
Serelaxin (RLX; synonyms: recombinant human relaxin, rhRLX) designates the pharmaceutical form of the human natural hormone relaxin-2 (RLX-2; H2 RLX) suitable for clinical use
Robust evidence has been accumulating that RLX can markedly reduce tissue and cell damage induced by ischemia and reperfusion (IR) [1,2,3]
Such a protective effect has been consistently observed in diverse experimental models, spanning from organ IR in whole animals [4,5,6,7,8] and in isolated and perfused organs [9,10,11,12] to specific cell types subjected to in vitro hypoxia and reoxygenation [13,14]
Summary
Serelaxin (RLX; synonyms: recombinant human relaxin, rhRLX) designates the pharmaceutical form of the human natural hormone relaxin-2 (RLX-2; H2 RLX) suitable for clinical use. Robust evidence has been accumulating that RLX can markedly reduce tissue and cell damage induced by ischemia and reperfusion (IR) [1,2,3] Such a protective effect has been consistently observed in diverse experimental models, spanning from organ IR in whole animals (heart, gut, kidney) [4,5,6,7,8] and in isolated and perfused organs (heart, lung, liver) [9,10,11,12] to specific cell types (cardiomyocytes, trophoblast) subjected to in vitro hypoxia (associated or not with nutrient starvation) and reoxygenation [13,14].
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