A novel protective formulation of Palmitoylethanolamide in experimental model of contrast agent induced nephropathy

Toxicol Lett. 2016 Jan 5;240(1):10-21. doi: 10.1016/j.toxlet.2015.10.006. Epub 2015 Oct 21.

Abstract

Contrast-induced nephropathy (CIN) is a complication in patients after administration of iodinated contrast media. Several risk factors contribute to the development and progression of CIN, including hypertension, diabetes, and dyslipidemia. Animal models of CIN by surgical intervention to reproduce its clinical and pathology has been developed, and thus, therapeutic methods tested. Palmitoylethanolamide (PEA) is a member of the fatty acid ethanolamine family with analgesic and anti-inflammatory effects. In this study, we analyzed streptozotocin-induced diabetes model and in an another set of experiment a surgical remotion of the kidney with the aim of evaluating effect of ultramicronized Palmitoylethanolamide (PEA-um(®)) on contrast induced renal disfunction and glomerular morphology alteration. In a first step of our study, we demonstrated that PEA-um(®) significantly reduced CIN-mediated glomerular dysfunction, modulates Na(+) and K(+) levels in plasma and decreased urine and plasma NGAL levels and α-GST urine levels. Moreover, in a second set of experiment we investigated how PEA-um(®) reduced creatinine and BUN plasma levels after nephrectomy, ameliorate renal and medullary blood flow and re-established renal parenchymal after CIN induction as well as after nephrectomy. Take together our results demonstrated that PEA-um(®) are able to preventing CIN in diabetic rats and alteration of biochemical parameters after nephrectomy.

Keywords: Contrast-induced nephropathy; Inflammation; Nephrectomy; Palmitoylethanolamide.

MeSH terms

  • Acute-Phase Proteins
  • Amides
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Urea Nitrogen
  • Contrast Media / administration & dosage
  • Contrast Media / adverse effects*
  • Creatinine / blood
  • Diabetes Mellitus, Experimental
  • Disease Models, Animal
  • Ethanolamines / pharmacology*
  • Glutathione Transferase / urine
  • In Situ Nick-End Labeling
  • Iohexol / administration & dosage
  • Iohexol / adverse effects
  • Iopamidol / administration & dosage
  • Iopamidol / adverse effects
  • Iopamidol / analogs & derivatives
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / surgery
  • Lipocalin-2
  • Lipocalins / blood
  • Male
  • Palmitic Acids / pharmacology*
  • Particle Size
  • Potassium / blood
  • Proto-Oncogene Proteins / blood
  • Rats
  • Rats, Wistar
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / drug therapy
  • Renal Insufficiency / pathology*
  • Sodium / blood
  • Streptozocin / administration & dosage
  • Streptozocin / adverse effects

Substances

  • Acute-Phase Proteins
  • Amides
  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Contrast Media
  • Ethanolamines
  • Lcn2 protein, rat
  • Lipocalin-2
  • Lipocalins
  • Palmitic Acids
  • Proto-Oncogene Proteins
  • iomeprol
  • Iohexol
  • Streptozocin
  • palmidrol
  • Sodium
  • Creatinine
  • Glutathione Transferase
  • Iopamidol
  • Potassium