Zinc oxide nanoparticles and spironolactone-enhanced Nrf2/HO-1 pathway and inhibited Wnt/β-catenin pathway in adenine-induced nephrotoxicity in rats

Redox Rep. 2022 Dec;27(1):249-258. doi: 10.1080/13510002.2022.2139947.

Abstract

Objective: To investigate the renoprotective, the antioxidant, and the anti-inflammatory impact of a combination of SPL and ZnO-NPs to combat against chronic kidney disease (CKD).

Methods: In total, 50 males of rats were distributed into 5 groups (10 rats each); normal group, adenine sulfate (0.25% in diet for 10 days) (CKD) group. After the last dose of adenine sulfate, rats were divided into three groups: SPL + Adenine sulfate group; rats were treated orally by mixing SPL (20 mg/kg/day) into chow for 8 weeks, ZnO-NPs + Adenine sulfate group; rats were injected intraperitoneally with ZnO-NPs (5 mg/kg) three times weekly for 8 weeks, ZnO-NPs + SPL + Adenine sulfate group; rats were injected with the same previous doses for 8 weeks.

Results: Each of SPL and ZnO-NPs up-regulated antioxidant genes (Nrf2 and HO-1), down-regulated fibrotic and inflammatory genes (TGF-β1, Wnt7a, β-catenin, fibronectin, collagen IV, α-SMA, TNF-α, and IL-6) compared to CKD. Furthermore, a combination of SPL and ZnO-NPs resulted in a greater improvement in the measured parameters than a single treatment.

Conclusion: The therapeutic role of SPL was enhanced by the antioxidant and the anti-inflammatory role of ZnO-NPs, which presented a great renoprotective effect against CKD.

Keywords: CKD; HO-1; Nephrotoxicity; Nrf2; Wnt; ZnO-NPs; spironolactone; β-catenin.

MeSH terms

  • Adenine / toxicity
  • Animals
  • Anti-Inflammatory Agents
  • Antioxidants / metabolism
  • Antioxidants / therapeutic use
  • Male
  • NF-E2-Related Factor 2
  • Nanoparticles*
  • Rats
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / drug therapy
  • Spironolactone
  • Sulfates
  • Zinc Oxide* / toxicity
  • beta Catenin

Substances

  • Zinc Oxide
  • Spironolactone
  • NF-E2-Related Factor 2
  • Antioxidants
  • Adenine
  • beta Catenin
  • Anti-Inflammatory Agents
  • Sulfates

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.