TY  - JOUR
AB  - Renal ischemia-reperfusion (IR) injury (IRI) is a common and important trigger of acute renal injury (AKI). It is inevitably linked to transplantation. Involving both, the innate and the adaptive immune response, IRI causes subsequent sterile inflammation. Attraction to and transmigration of immune cells into the interstitium is associated with increased vascular permeability and loss of endothelial and tubular epithelial cell integrity. Considering the important role of cytoskeletal reorganization, mainly regulated by RhoGTPases, in the development of IRI we hypothesized that a preventive, selective inhibition of the Rho effector Rho-associated coiled coil containing protein kinase (ROCK) by hydroxyfasudil may improve renal IRI outcome. Using an IRI-based animal model of AKI in male Sprague Dawley rats, animals treated with hydroxyfasudil showed reduced proteinuria and polyuria as well as increased urine osmolarity when compared with sham-treated animals. In addition, renal perfusion (as assessed by 18F-fluoride Positron Emission Tomography (PET)), creatinine- and ureaclearances improved significantly. Moreover, endothelial leakage and renal inflammation was significantly reduced as determined by histology, 18F-fluordesoxyglucose-microautoradiography, Evans Blue, and real-time PCR analysis. We conclude from our study that ROCK-inhibition by hydroxyfasudil significantly improves kidney function in a rat model of acute renal IRI and is therefore a potential new therapeutic option in humans.
AU  - Kentrup, Dominik
AU  - Kentrup, Dominik Richard
AU  - Reuter, Stefan Johannes
AU  - Schnöckel, Uta
AU  - Grabner, Alexander
AU  - Edemir, Bayram
AU  - Pavenstädt, Hermann-Joseph
AU  - Schober, Otmar
AU  - Schober, O.
AU  - Schäfers, Michael
AU  - Schlatter, Eberhard
AU  - Büssemaker, Eckhart
AU  - Büssemaker, Eckhart Ulrich
DA  - 2011-10-21
DO  - doi:10.1371/journal.pone.0026419
LA  - eng
N1  - Finanziert durch den Open-Access-Publikationsfonds 2011/2012 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - PLoS ONE 6 (2011) 10, e26419
PY  - 2011-10-21
TI  - Hydroxyfasudil-Mediated Inhibition of ROCK1 and ROCK2 Improves Kidney Function in Rat Renal Acute Ischemia-Reperfusion Injury
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-77379454716
Y2  - 2024-11-22T03:02:02
ER  -