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Abstract: SA-PO087

A Short Treatment With Resveratrol After Ischemia/Reperfusion Injury Prevents Maladaptive Repair and Long-Term CKD

Session Information

  • AKI: Mechanisms - III
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Martinez-Rojas, Miguel Angel, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Ciudad de México, Mexico
  • Gonzalez Rivera, Jesus Manuel, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Ciudad de México, Mexico
  • Ponce Nava, Maria Susana, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Ciudad de México, Mexico
  • Pérez-Villalva, Rosalba, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Ciudad de México, Mexico
  • Bobadilla, Norma, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Ciudad de México, Mexico
Background

Acute Kidney Injury (AKI) leads to Chronic Kidney Disease (CKD) through maladaptive repair. The reversibility of this process after AKI has occurred remains unclear. Treatment with resveratrol (RSV) before AKI ameliorates renal dysfunction through multiple mechanisms. We aimed to evaluate if a transient administration of RSV after ischemia/reperfusion injury (IRI) is enough to prevent CKD.

Methods

Eighteen male Wistar rats weighting 300-350 g were randomized in three groups: Sham surgery, IRI for 30 min (IRI), and IRI + RSV. Daily treatment with RSV was initiated 24 h after IRI and maintained only 10 days. Rats were followed for 5 months. Proteinuria was determined monthly, while kidney function and fibrosis were evaluated at the 5th month. To study early reparative process, another 18 rats were included with the same design but euthanized at the 10th day. Histologic changes were evaluated with Sirius Red and PAS stains. Gene expression was evaluated with RT-qPCR and Western blot. Differences between groups were analyzed through ANOVA and post-hoc testing with a significance level of p<0.05.

Results

Treatment with RSV prevented late CKD as indicated by proteinuria, creatinine clearance and tubule-interstitial fibrosis. Despite having a severe initial AKI, rats receiving RSV for only 10 days after IRI improved drastically kidney histological changes and expression of Il6, Tnfa, Ccl2, Il10, Tgfb1, Mrc1 compared to the IRI group, indicating accelerated immune cells clearance. This was accompanied by reduced levels of NFkB-p65. Also, RSV prevented the typical raise in tubular injury-related genes and recovered Sirt3, FoxO3, and catalase expression, leading to a lesser oxidative stress compared to IRI group.

Conclusion

A short treatment with RSV after IRI is enough to prevent maladaptive reapir and CKD in rats. This renoprotective effect is mediated by a marked reduction in the inflammatory process, tubular injury, and oxidative stress. These findings highlight the relevance of the initial days of reperfusion, indicating that adaptive repair can be induced after severe AKI.

Funding

  • Government Support – Non-U.S.