{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:04:06Z","timestamp":1789243446510,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,6]],"date-time":"2015-12-06T00:00:00Z","timestamp":1449360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Despite the fact that the pathogenesis of aristolochic acid (AA) nephropathy is still unclear, we sought to determine whether nitric oxide is involved in the underlying mechanism of AA\u2010induced acute kidney injury (AKI).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Using a model of progressive tubulointerstitial nephritis, in which AA nephropathy exhibits two interconnected phases, an acute phase and a chronic phase of injury, we demonstrated that maintenance of nitric oxide bioavailability is essential to improve the outcome of AA\u2010induced AKI.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Aristolochic acid (AA) nephropathy (AAN), a progressive tubulointerstitial injury of toxic origin, is characterized by early and transient acute tubular necrosis. This process has been demonstrated to be associated with reduced nitric oxide (NO) production, which can disrupt the regulation of renal function. In this study, we tested the hypothesis that <jats:sc>l<\/jats:sc>\u2010arginine (<jats:sc>l<\/jats:sc>\u2010Arg) supplementation could restore renal function and reduce renal injury after AA intoxication. C57BL\/6\u00a0J male mice were randomly subjected to daily i.p. injection of either sterile saline solution or AA (2.5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) for 4\u00a0days. To determine whether AA\u2010induced renal injuries were linked to reduced NO production, <jats:sc>l<\/jats:sc>\u2010Arg, a substrate for NO synthase, was supplemented (5%) in drinking water. Mice intoxicated with AA exhibited features of rapid\u2010onset acute kidney injury, including polyuria, significantly increased plasma creatinine concentrations, proteinuria and fractional excretion of sodium (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), along with severe proximal tubular cell injury and increased NADPH oxidase 2 (Nox2)\u2010derived oxidative stress (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). This was associated with a significant reduction in NO bioavailability. <jats:sc>l<\/jats:sc>\u2010Arg supplementation in AA\u2010treated mice significantly increased NO bioavailability, which in turn improved renal function (creatininaemia, polyuria, proteinuria, fractional excreted sodium and <jats:italic>N<\/jats:italic>\u2010acetyl\u2010\u03b2\u2010<jats:sc>d<\/jats:sc>\u2010glucosaminidase enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis). These changes were associated with significant reductions in <jats:italic>Nox2<\/jats:italic> expression and in production of reactive oxygen species and with an increase in antioxidant concentrations. Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA\u2010induced acute kidney injury by reducing oxidative stress and maintaining renal function.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep085333","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T08:50:47Z","timestamp":1444207847000},"page":"193-206","source":"Crossref","is-referenced-by-count":35,"title":["Protective effect of nitric oxide in aristolochic acid\u2010induced toxic acute kidney injury: an old friend with new assets"],"prefix":"10.1113","volume":"101","author":[{"given":"Anne\u2010\u00c9milie","family":"Decl\u00e8ves","sequence":"first","affiliation":[{"name":"Molecular Physiology Research Unit\u2010URPHYM University of Namur (UNamur)  B\u20105000 Namur Belgium"},{"name":"Laboratory of Experimental Nephrology, Faculty of Medicine Universit\u00e9 Libre de Bruxelles (ULB)  B\u20101070 Brussels 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