[en] Abstract
BACKGROUND:
Aristolochic acid 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 NO production which can disrupt the regulation of renal function. This study tested the hypothesis that L-Arginine (L-Arg) supplementation could restore renal function and reduce renal injury after AA intoxication.
METHODS:
C57BL/6 J male mice were randomly subjected to intraperitoneal injection of either sterile saline solution or AA (2.5 mg kg-1 ) for 4 days. To determine whether AA-induced renal injuries were linked to reduced NO production, L-Arg, a substrate for NO synthase, was supplemented in drinking water (5%).
RESULTS:
Mice intoxicated with AA exhibited features of rapid onset AKI including polyuria, significantly increased plasma creatinine levels, proteinuria, and FENa (P < 0.05) along with severe proximal tubular cell injury and increased NOX2-derived oxidative stress (P < 0.05). This was associated with a significant reduction in NO bioavailability. L-Arg supplementation in AA-treated mice significantly increased NO bioavailability, which in turn improved renal function (creatininemia, polyuria, proteinuria, FENa, and NAG enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis). These changes were associated with significant reductions in Nox2 expression, and reactive oxygen species (ROS) production, and an increase in antioxidant levels.
CONCLUSIONS:
Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA-induced AKI by reducing oxidative stress and maintaining renal function. This article is protected by copyright. All rights reserved.
Research center :
UMHAP - Centre de Recherche UMONS-Ambroise Paré
Disciplines :
Endocrinology, metabolism & nutrition General & internal medicine Immunology & infectious disease Urology & nephrology
Author, co-author :
Decleves, Anne-Emilie ; Université de Mons > Faculté de Médecine et de Pharmacie > Biochimie métabolique et moléculaire
Jadot, I
Colombaro, V
Voisin, V
Habsch, I
De Prez, E
Nortier, J
Caron, N
Language :
English
Title :
Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury. An old friend with new assets
Publication date :
07 October 2015
Journal title :
Experimental Physiology
ISSN :
0958-0670
Publisher :
Blackwell, Oxford, United Kingdom
Volume :
101
Issue :
1
Pages :
193-206
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
M122 - Biochimie métabolique et moléculaire
Research institute :
R550 - Institut des Sciences et Technologies de la Santé
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