ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO168

pNaKtide Ameliorates Systemic Inflammatory Response in Murine Model of Sepsis by Antagonism of Na,K-ATPase Signaling

Session Information

  • AKI: Mechanisms - II
    November 04, 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

  • Pereira, Duane Gischewski, Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Pillai, Sneha S., Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Chaudhry, Muhammad A., Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Shapiro, Joseph I., Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
  • Sodhi, Komal, Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, United States
Background

Inflammatory processes and oxidative stress play a central role in the development and progression of sepsis, which can lead to multiple organ dysfunction. Hence, the use of strategies to limit this systemic inflammatory response, can be interesting in the development of an effective sepsis therapy. In this context, our research group recently demonstrate that the NaK-ATPase signaling can exacerbate inflammation and oxidative stress process and that pNaKtide, an antagonist of NaK-ATPase, is able to improve pathophysiological abnormalities. The objective of this work is to demonstrate the involvement of NaK-ATPase signaling in increase inflammatory response and oxidative stress and to demonstrate the effect of pNaKtide administration in experimental model of sepsis, induced by cecal ligation and puncture (CLP), as a drug against septic shock.

Methods

Male C57BL6 mice were used to induced experimental sepsis by CLP with or without, IP administration of pNaKtide (25mg/kg body wt) 24h before CLP surgery. Sham surgeries were performed and used as control for the CLP model. The severity of sepsis was assessed using the Murine Sepsis Score (MSS) at baseline, 4h, 8h and 24h after surgery for Sham and CLP. After 24h of Sham or CLP surgeries the mice were euthanized, blood was used for analysis of inflammatory markers and kidney was collected for biochemistry and morphological analysis.

Results

Systemic administration of pNaKtide was able to significantly improve the MSS after CLP surgery, as compared to CLP mice without pNaKtide injection. Histological analysis of kidney tissues by H&E staining showed a decrease in congestion, inflammatory infiltrate and hemorrhage in CLP mice with pNaKtide injection, as compared to CLP. As well, improved mRNA expression of inflammatory and macrophage infiltration markers, in kidney tissues of CLP mice. The pNaKtide administration also improved plasma levels of creatinine and urea, markers of kidney function.

Conclusion

Our study demonstrated that antagonism of Na,K-ATPase signaling by pNaKtide can attenuate the progression of CLP-induced sepsis by inhibiting the inflammatory process usually noted in this condiction. Therefore, Na,K-ATPase signaling may serve as a viable clinical target for therapeutic intervention of sepsis and associated inflammatory mechanisms.

Funding

  • Other NIH Support