Protective effect of oral L-arginine supplementation on cyclosporine induced nephropathy in rats

dc.authoridEşrefoğlu, Mukaddes/0000-0003-3380-1480
dc.authoridbay karabulut, aysun/0000-0002-7873-2805;
dc.authorwosidEşrefoğlu, Mukaddes/JWA-4590-2024
dc.authorwosidbay karabulut, aysun/HJP-0995-2023
dc.authorwosidOzturk, Feral/A-2678-2016
dc.contributor.authorKurus, Meltem
dc.contributor.authorEsrefoglu, Mukaddes
dc.contributor.authorBay, Aysun
dc.contributor.authorOzturk, Feral
dc.date.accessioned2024-08-04T20:15:06Z
dc.date.available2024-08-04T20:15:06Z
dc.date.issued2005
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: One of the major adverse effects of long term cyclosporine A ( CyA) administration is chronic nephrotoxicity. Several studies have suggested that alterations of the L-arginine (L-Arg) nitric oxide ( NO) pathway may be involved in the pathogenesis of CyA-induced kidney damage. Aim: We postulated that in vivo activation of L-Arg-NO pathway might have a beneficial effect on CyA-induced renal damage. Conditions of chronic NO enhancement was established with L-Arg supplementation and chronic NO blockade with N-nitro-L-Arg methyl ester ( L- NAME). We tested the hypothesis that, if CyA administration alters intrarenal NO synthesis, then exogenous L-Arg supplementation could limit renal injury, on the contrary, L- NAME, a potent competitive inhibitor of NO synthesis, could enhance CyA nephrotoxicity. Harmful effect of NO blockade indirectly supports the beneficial effect of NO in a model of CyA nephrotoxicity. Methods: Rats were administered vehicle (VH), CyA (7.5 mg/kg/day), CyA + L-Arg (2g/kg/day), CyA + L- NAME (5 mg/100ml/day), CyA + L-Arg + L- NAME, VH + L-Arg, VH + L-NAME and were sacrificed at the end of the experiment. Body weight, serum creatinine, blood urea nitrogen ( BUN) and NO levels were determined. Tubular injury and interstitial fibrosis were evaluated semiquantitatively using scoring systems on paraffin sections stained with hematoxylin/eosin (H/E), Masson's trichromic and periodic acid-Schiff (PAS). Results: The CyA group developed marked renal injury, characterized by a significant increase in serum creatinine and BUN, and histopathological alterations including tubular dilatation, vacuolization, necrosis, interstitial cell infiltration and tubulointerstitial fibrosis. CyA reduced serum NO level. L-Arg treatment significantly enhanced NO biosynthesis and protected animals from CyA-induced kidney damage. In contrast L- NAME strikingly reduced serum NO level, and worsened biochemical and histopathological alterations. Conclusion: Chronic CyA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement suggesting that L-Arg supplementation may be protective in CyA nephrotoxicity.en_US
dc.identifier.doi10.1007/s11255-004-0011-5
dc.identifier.endpage594en_US
dc.identifier.issn0301-1623
dc.identifier.issn1573-2584
dc.identifier.issue3en_US
dc.identifier.pmid16307347en_US
dc.identifier.scopus2-s2.0-28844444512en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage587en_US
dc.identifier.urihttps://doi.org/10.1007/s11255-004-0011-5
dc.identifier.urihttps://hdl.handle.net/11616/94180
dc.identifier.volume37en_US
dc.identifier.wosWOS:000202943700034en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofInternational Urology and Nephrologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectcyclosporine Aen_US
dc.subjecthistopathologyen_US
dc.subjectL-arginineen_US
dc.subjectnephrotoxicityen_US
dc.subjectnitric oxideen_US
dc.subjectN-nitro-L-arginine methyl esteren_US
dc.titleProtective effect of oral L-arginine supplementation on cyclosporine induced nephropathy in ratsen_US
dc.typeArticleen_US

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