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

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.

Pentosan Polysulfate Treatment of Mucopolysaccharidosis Type IIIA Mice

“…Previous studies from our lab and others have shown that PPS has potent anti-inflammatory properties in various disease models and patients (e.g., Schuchman et al 2013;Frohbergh et al 2014;Simonaro et al 2016;Hardi et al 2016;Sanden et al 2017;Hennermann et al 2016). Consistent with these reports, once weekly subQ PPS administration to MPS IIIA mice attenuated systemic inflammation, as shown by the reduction of the elevated plasma inflammatory markers IL-1a, MCP-1, MIP-1a, and G-CSF (Fig.…”

“…As shown in Supplementary Fig. 2, we did observe reductions in liver or spleen GAGs in the treated mice, although we hypothesize that this is due to the remaining PPS and the fact that the drug is known to accumulate in these tissues after injection (Greenslade et al 1983). In contrast, in the spleen where less residual PPS will be present, significant GAG reductions were observed.…”

Association of Extracellular Vesicle Protein Cargo with Race and Clinical Markers of Mortality

“…This could be particularly relevant given that AAs are at highest risk for End Stage Renal Disease. For example, phospho-p53 has been associated with DNA damage and inflammation in rodent models of acute kidney injury and diabetic kidney disease 29–32 . Higher levels of cleaved caspase 3 have also been reported in these rodent models 29–31 .…”

Pentosan polysulfate ameliorates fibrosis and inflammation markers in SV40 MES13 cells by suppressing activation of PI3K/AKT pathway via miR-446a-3p

“…Pentosan polysulphate sodium (PPS) is a nonselective anti-inflammatory agent approved by the FDA as the only oral medication for the treatment of interstitial cystitis [ 11 ]. PPS has been shown to improve renal function and fibrosis in 5/6 nephrectomized rats [ 12 ] and ischemia/reperfusion-injured rats [ 13 ]. However, whether PPS protects against diabetic renal fibrosis and the underlying mechanism by which PPS protects against renal injury remain unknown.…”