Abstract: TH-PO409

pNaKtide Attenuates Kidney Dysfunction and Systemic Inflammation by Blocking Na/K-ATPase/Reactive Oxygen Species Amplification in ApoE -/- Mice

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Nawab, Athar, Marshall Health, Morgantown, West Virginia, United States
  • Snoad, Brian J, Marshall University, Huntington, West Virginia, United States
  • Lakhani, Hari Vishal, Marshall University, Huntington, West Virginia, United States
  • Sodhi, Komal, Marshall University, Huntington, West Virginia, United States
  • Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States
Background

We have previously reported that the alpha-1 subunit of the sodium potassium adenosine triphosphatase (Na/K-ATPase) acts as an amplifier for reactive oxygen species (ROS) in addition to its ion pumping function. We have also shown that blockade of this amplification with a novel peptide, pNaKtide, ameliorates oxidative stress and obesity in mice subjected to a high-fat diet.

Methods

pNaKtide was administered in ApoE knockout mouse fed western diet. 25 mg/Kg pNaKtide was administered intraperitoneally once every 7 days for 2 months. Lipid profile, ROS levels and plasma creatinine were measured Also, kidney fibrosis was quantified.

Results

pNaKtide administered to these mice significantly decreased plasma triglycerides, FFA, and LDL levels (p<0.05). Further, our results show that ApoE -/- mice fed a western diet had decreased plasma HDL levels and this decrease was reversed by pNaKtide. Plasma ROS levels were also significantly attenuated by pNaKtide treatment. Our results show that pNaKtide improved plasma creatinine and kidney fibrosis in in ApoE-/- mice fed a western diet (p<0.05

Conclusion

This study suggests that the Na/K-ATPase/ROS signaling cascade is a possible mechanism for the development of kidney dysfunction and systemic inflammation associated with the metabolic syndrome phenotype and pNaKtide presents a potential novel treatment for these pathologies.