Open AccessAcute treatment with relaxin protects the kidney against ischaemia/reperfusion injury
Author(s) -
Collino Massimo,
Rogazzo Mara,
Pini Alessandro,
Benetti Elisa,
Rosa Arianna Carolina,
Chiazza Fausto,
Fantozzi Roberto,
Bani Daniele,
Masini Emanuela
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12120
Subject(s) - acute kidney injury , kidney , medicine , oxidative stress , nitric oxide synthase , pharmacology , lipid peroxidation , nitric oxide , creatinine , superoxide dismutase , endocrinology , nephrotoxicity , reperfusion injury , ischemia
Abstract Although recent preclinical and clinical studies have demonstrated that recombinant human relaxin (rh RLX ) may have important therapeutic potential in acute heart failure and chronic kidney diseases, the effects of acute rh RLX administration against renal ischaemia/reperfusion (I/R) injury have never been investigated. Using a rat model of 1‐hr bilateral renal artery occlusion followed by 6‐hr reperfusion, we investigated the effects of rh RLX (5 μg/Kg i.v.) given both at the beginning and after 3 hrs of reperfusion. Acute rh RLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N ‐acetyl‐β‐glucosaminidase) evoked by renal I/R. These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical‐induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes Mn ‐ and CuZn ‐superoxide dismutases ( SOD ). Furthermore, rh RLX administration attenuated the increase in leucocyte activation, as suggested by inhibition of myeloperoxidase activity, intercellular‐adhesion‐molecule‐1 expression, interleukin ( IL )‐1β, IL ‐18 and tumour necrosis factor‐α production as well as increase in IL ‐10 production. Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rh RLX ‐induced activation of endothelial nitric oxide synthase and up‐regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal‐regulated protein kinase (ERK) 1/2, respectively. Thus, we report herein that rh RLX protects the kidney against I/R injury by a mechanism that involves changes in nitric oxide signalling pathway.