Abstract: TH-PO251

Involvement of Sirtuins 1 and 3 during the Acute Phase of Aristolochic Acid Nephropathy

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic


  • Jadot, Inès, University of Namur, Namur, Belgium
  • Mosseray, Pauline Florence, University of Namur, Namur, Belgium
  • Martin, Blanche, University of Namur, Namur, Belgium
  • Botton, Olivia, University of Namur, Namur, Belgium
  • Nortier, Joelle L., Hospital Erasme, Brussels, Belgium
  • Decleves, Anne-Emilie, Laboratory of Molecular Biology, University of Mons, Belgium, NIMY (MONS), Belgium
  • Arnould, Thierry, University of Namur, Namur, Belgium
  • Caron, Nathalie, University of Namur, Namur, Belgium

Aristolochic acid (AA) nephropathy (AAN) is a rapidly progressive tubulointerstitial nephritis induced by intoxication with AA and is usually associated with end-stage renal disease and urothelial malignancy. While the carcinogenic mechanisms of AA have been well documented, the mechanisms by which AA exert cytotoxic effects on proximal tubular epithelial cells, AA’s primary target, are poorly characterized. Since oxidative stress and mitochondrial damage are known to be drivers of acute kidney injury, the goal of this study is to characterize oxidative stress and mitochondrial dysregulation with a particular emphasis on sirtuins (SIRT) during the acute phase of experimental AAN. Indeed, SIRT1 and SIRT3 have been previously described to be protective in different models of kidney disease. Therefore, this study aims to investigate for the first time the involvement of SIRT1 and SIRT3 in the pathophysiology of AAN.


C57BL/6J male mice were randomly subjected to daily i.p. injection of AAI (3,5mg/kg) for 4 days. Mice were euthanized 24 hours, 5 days and 10 days after the beginning of AA intoxication.


Polyuria and proteinuria were observed 5 days after AA intoxication as well as an increase in plasma creatinine and in blood urea nitrogen confirming renal failure. Histological analysis revealed early alterations of proximal tubules 24 hours after AA intoxication. At day 5, necrotic tubules with cellular debris in the tubular lumen were observed thereafter evolving at day 10 to atrophic tubules. Tubular injury was confirmed by upregulation of relative mRNA expression of NGAL. Along with renal failure, inflammation developed with upregulation of mRNA of inflammatory cytokines (MCP1, MIP2, IL1β, IL6 and TNFα) and with macrophage infiltration. Antioxidant pathways were also downregulated as attested by decrease in mRNA expression of NRF-2 and SOD at day 5 and day 10. Finally, relative mRNA expression of SIRT1 and SIRT3 was found to be downregulated from day 5 until day 10, the protein expression of SIRT3 being also reduced at the same time-points.


The downregulation of SIRT1 and SIRT3 observed in the acute phase of AAN could constitute a key event in AAN pathogenesis. Therefore, this observation could lead to a new potential strategy for improving outcomes of AAN.


  • Government Support - Non-U.S.