Abstract: TH-PO325

Ala-Apelin, an Apelin Receptor Antagonist, Ameliorates Contrast-Induced Nephropathy in Rats

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration

Authors

  • Kutlug Agackiran, Seda, Marmara University Medical Faculty, Department of Internal Medicine, Istanbul, Turkey
  • Shbair, Abdullah, Marmara University Medical Faculty, 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, Marmara University Medical Faculty, 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. Mechanisms of CIN include renal vasoconstriction, medullary hypoxia, endothelial injury, oxidative stress and direct tubular toxicity of contrast agents. Apelin (Ap) is a vasodilatatory molecule and has been shown to prevent cardiac ischemia-reperfusion injury. On the contrary, ala-apelin (Ala-Ap), an apelin receptor antagonist, has anti-fibrotic effects on CCl4 induced liver fibrosis. In this study, we aimed to demonstrate the effects of Ap and Ala-Ap 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 Ap (100 mcg/kg/day, n=8) or Ala-Ap (100 mcg/kg/day, n=8) 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, Ap and Ala-Ap-treated groups were elevated as compared to control group (p<0.05, 0.001 and 0.001), while the increases in serum creatinine in Ala-Ap-treated group was significantly lower as compared to Ap-treated group (p<0.05). In contrast to depressed 24-h creatinine clearance in SL and Ap-treated groups (p<0.01), creatinine clearance in Ala-Ap-treated group was similar to control group (p=0.25). CIN-induced increase in renal myeloperoxidase activity in SL-treated group (p<0.01) was abolished in Ala-Ap-treated group (p<0.05), while renal glutathione content was increased with Ala-Ap treatment (p<0.01). However, histopathological damage scores obtained by light microscopic examination were lower in both Ap and ala-Ap-treated groups as compared to SL-treated group (p<0.01).

Conclusion

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

Funding

  • Government Support - Non-U.S.