The protective effect of erdosteine on radiocontrast induced nephrotoxicity in rats

Environ Toxicol. 2011 Aug;26(4):395-402. doi: 10.1002/tox.20691. Epub 2011 Mar 7.

Abstract

Acute renal failure resulting from radiocontrast-induced nephrotoxicity (RIN) is suggested to occur via medullary ischemia coupled with the generation of free radicals and oxidative injury to tubular cells. The aim of the present study was to assess the effects of erdosteine on prevention of RIN. Thirty-three Wistar-albino rats were divided into five groups: control (group 1, n = 6), radiocontrast media (group 2, n = 6), erdosteine (group 3, n = 7), erdosteine four doses before radiocontrast application (group 4, n = 7) and erdosteine one dose at the same day with radiocontrast application (group 5, n = 7). RIN was induced by administration of intravenous high osmolar contrast media amidotrizoate (6 mL/kg). Total RNA was extracted from the kidney, and the expression levels of Lipocalin 2 (Lcn2) and secreted phosphoprotein 1 (Spp1) genes were evaluated by real time reverse transcription polymerase chain reaction (real-time RT-PCR). Total antioxidant status (TAS) and total oxidant status (TOS) were measured in kidney homogenates and serum samples. Serum creatinine, BUN (Blood Urea Nitrogen) and cystatin-C levels were measured from serum samples. The kidneys were evaluated histopathologically. The expression levels of Spp1 and Lcn2 genes in group 2 were significantly higher than groups 1, 3, 4, and 5. The expression levels of Spp1 and Lcn2 genes in group 4 were four and two times lower than group 5, respectively. Kidney TOS levels in group 2 were significantly higher than groups 1, 3, 4, and 5. Kidney TAS levels in group 3 were higher than group 2. Kidney oxidative stress index (OSI) levels in group 2 were significantly higher than groups 4 and 5. All rats in contrast media group developed tubular necrosis, proteinaceous casts, medullary congestion although these changes were significantly reduced in groups 4 and 5. This study demonstrated that multiple doses of erdosteine before application may have higher protective effects against RIN.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Blood Urea Nitrogen
  • Contrast Media / toxicity*
  • Creatinine / blood
  • Cystatin C / blood
  • Female
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipocalins / genetics
  • Lipocalins / metabolism
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • Oxidants / metabolism
  • Oxidants / toxicity
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thioglycolates / pharmacology*
  • Thiophenes / pharmacology*
  • Xenobiotics / toxicity*

Substances

  • Antioxidants
  • Contrast Media
  • Cystatin C
  • Lipocalins
  • Oxidants
  • Thioglycolates
  • Thiophenes
  • Xenobiotics
  • Osteopontin
  • erdosteine
  • Creatinine