Erythropoietin attenuates LPS-induced microvascular damage in a murine model of septic acute kidney injury

STOYANOFF, TANIA ROMINA; RODRÍGUEZ, JUAN PABLO; TODARO, JUAN SANTIAGO; MELANA COLAVITA, JUAN PABLO; TORRES, ADRIANA MÓNICA; AGUIRRE, MARÍA VICTORIA

BIOMEDICINE & PHARMACOTHERAPY = BIOMEDECINE & PHARMACOTHERAPIE.

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Año: 2018 vol. 107 p. 1046 - 1055

0753-3322

Acute kidney injury (AKI) is a frequent complication of sepsis, with a high mortality. Hallmarks of septic-AKIinclude inflammation, endothelial injury, and tissue hypoxia. Therefore, it would be of interest to developtherapeutic approaches for improving the microvascular damage in septic-AKI. Erythropoietin (EPO) is a wellknowncytoprotective multifunctional hormone. Thus, the aim of this study was to evaluate the protective effectsof EPO on microvascular injury in a murine model of endotoxemic AKI.Male Balb/c mice were divided into four groups: control, LPS (8 mg/kg, ip.), EPO (3000 IU / kg, sc.) andLPS+EPO. A time course study (0?48 h) was designed. Experiments include, among others, immunohistochemistryand Western blottings of hypoxia-inducible transcription factor (HIF-1α), erythropoietinreceptor (EPO-R), vascular endothelial growth factor system (VEGF/VEGFR-2), platelet and endothelial adhesionmolecule-1 (PeCAM-1), inducible nitric oxide synthase (iNOS) and phosphorylated nuclear factor kappa B p65(NF-κB).Data showed that EPO attenuates renal microvascular damage during septic-AKI progression through a) thedecrease of HIF-1 alpha, iNOS, and NF-κB and b) the enhancement of EPO-R, PeCAM-1, VEGF, and VEGFR-2expression.In summary, EPO renoprotection involves the attenuation of septic-induced renal hypoxia and inflammationas well as ameliorates the endotoxemic microvascular injury.