DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2015-11-03 - Colloque/Article dans les actes avec comité de lecture - Anglais - 1 page(s)

Jadot Ines, Decleves Anne-Emilie , Colombaro V, Martin Blanche, Habsch Isabelle, De Prez Eric, Nortier Joëlle, Caron Nathalie, "Protective Effect of Nitric Oxide in Aristolochic Acid-Induced Toxic Acute Kidney Injury" in American Society of Nephrology, 26, 887A, San Diego, Etats-Unis, 2015

  • Codes CREF : Néphrologie - urologie (DI3325), Pathologies particulières (DI3370)
  • Unités de recherche UMONS : Biologie moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Mind & Health (CREMH)

Abstract(s) :

(Anglais) Background: Aristolochic Acid (AA) nephropathy is a pertinent example of tubulo‑ interstitial (TI) nephritis characterized by an early phase of acute kidney injury (AKI) leading to progressive fibrosis and chronic kidney disease (CKD). Nitric oxide (NO) has been shown to play a critical role in the AKI‑to‑CKD transition. Here, the AAN model was used to determine the role of NO in this process, focusing on the acute phase. Methods: C57BL/6J male mice were randomly subjected to daily i.p. injection of control solution or AAI (3,5mg/kg) for 4 days and L-Arginine (L-Arg; substrate for NO synthesis) was supplemented in drinking water (5%) until mice were euthanized, 5 days after the beginning of AAI injections. Results: At day 5, AA‑treated mice displayed polyuria, increased plasma creatinine level and proteinuria. In addition, histological analyses revealed severe proximal tubular cell necrosis, renal inflammation and increased oxidative stress in AA-treated mice. These changes were associated with a significant reduction of NO bioavailability, as attested by urinary NOx and cGMP levels. L-Arg supplementation in AA-treated mice significantly improved kidney function, as reported by a significant reduction in urine volume, plasma creatinine level and proteinuria. Moreover, L-Arg treatment resulted in a significant reduction of tubular cell necrosis, renal inflammation and oxidative stress. These were concomitant to normalized NO levels. Conclusions: Our findings demonstrated that sustaining NO bioavailability due to L-Arg supplementation improve the renal outcome of AA-induced AKI phase. Further investigations are ongoing to determine whether increasing NO bioavailability can also prevent chronic injuries in the AAN model.