Sodium Pentosan Polysulfate Reduced Renal Ischemia-Reperfusion-Induced Oxidative Stress and Inflammatory Responses in an Experimental Animal Model

J Vasc Res. 2016;53(3-4):230-242. doi: 10.1159/000452246. Epub 2016 Nov 26.

Abstract

Acute kidney injury (AKI) remains an independent risk factor for mortality and morbidity after vascular surgery (affecting the renal arteries) or aortic surgery (requiring suprarenal aortic clamping). These types of vascular surgery produce renal ischemia/reperfusion (I/R) injury, a common cause of AKI. The present studies aimed at monitoring the course of renal I/R injury at the cellular level and investigating the efficacy of long-term preoperative and single-shot intraoperative administration of sodium pentosan polysulfate (PPS) to protect renal tissue from acute I/R injury both in native and diabetic kidneys in rats. Western blot analyses of the proapoptotic (bax) and antiapoptotic (bcl-2) signaling pathways, as well as the extent of DNA damage (phospho-p53), were performed. Oxidative stress followed upon the termination of malondialdehyde, reduced glutathione, thiol group, and superoxide dismutase plasma levels. Inflammatory changes were measured by the determination of serum tumor necrosis factor-α and interleukin-1 levels. Morphological changes were detected by histological examinations. Our results showed that the long-term administration of PPS has an advantage in reducing I/R kidney injury in diabetic rats, while high-dose, single-shot parenteral administration of PPS prior to revascularization might be useful in nondiabetic rats.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers / blood
  • DNA Damage
  • Diabetes Mellitus, Experimental
  • Inflammation Mediators / blood*
  • Interleukin-1 / blood
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress / drug effects*
  • Pentosan Sulfuric Polyester / pharmacology*
  • Rats, Wistar
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Inflammation Mediators
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Pentosan Sulfuric Polyester