Abstract: TH-PO342

Sphingosine-1 Receptor Agonist SEW2871 Ameliorates Contrast-Induced Nephropathy in Rats

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration

Authors

  • Shbair, Abdullah, Department of Internal Medicine, Istanbul, Turkey
  • Kutlug Agackiran, Seda, Department of Internal Medicine, Istanbul, Turkey
  • Ozdemir, Zarife, Marmara University Medical Faculty, Department of Physiology, Istanbul, Turkey
  • Cilingir Kaya, Ozlem Tugce, Marmara University Medical Faculty, Department of Histology, Istanbul, Turkey
  • Ozkan, Naziye, Marmara University Medical Faculty, Department of Histology, Istanbul, Turkey
  • Cetinel, Sule, Marmara University Medical Faculty, Department of Histology, Istanbul, Turkey
  • Yegen, Berrak, Marmara University Medical Faculty, Department of Physiology, Istanbul, Turkey
  • Koc, Mehmet, Department of Internal Medicine, Istanbul, Turkey
Background

With a dramatically increasing incidence in today’s medicine, contrast-induced nephropathy (CIN) is the third common cause of acute kidney injury (AKI). Mechanisms of CIN include renal medullary hypoxia, endothelial injury, oxidative stress and direct tubular toxicity of contrast agents. A sphingosine-1 receptor agonist SEW2871 has been shown to prevent ischemia-induced AKI. In this study, we aimed to demonstrate the effects of SEW2871 on CIN.

Methods

Male Sprague-Dawley rats were injected intraperitoneally with only saline (control group, n=8), while CIN groups were treated with either saline (SL, n=9) or SEW2871 (10 mg/kg/day, n=7) at 0, 24 and 48 hours of the experiment. CIN was established by intravenously injecting indomethacin (10 mg/kg), L-NAME (10 mg/kg) and a high-osmolar contrast agent (Urografin 76%, 6 ml/kg) at 24th h of the experiment. On the 72nd h, kidneys were removed for the assessment of histopathological changes and the determination of glutathione levels and myeloperoxidase activity. Data were analyzed using ANOVA and Student’s t-test.

Results

Serum creatinine and BUN levels in SL- and SEW2871-treated CIN groups were elevated as compared to control group (p<0.05-0.01), while the increases in SEW2871-treated group were relatively lower. In contrast to depressed 24-h creatinine clearance in SL-treated CIN group (p<0.05), clearance in SEW2871-treated group was not different than that of the control group. CIN-induced increase in renal myeloperoxidase activity (p<0.01) was abolished in SEW2871-treated group (p<0.05), while renal glutathione content was increased with SEW2871 (p<0.001). However, histopathological damage scores obtained by light microscopic examination were similar in SEW2871- or SL-treated CIN groups.

Conclusion

The present data demonstrate that CIN is ameliorated by administration of SEW2871, which appears to act, in part, by diminishing oxidative stress via the inhibition of neutrophil infiltration.

Funding

  • Government Support - Non-U.S.