Serum and Tissue HIF-2 Alpha Expression in CIN, N-Acetyl Cysteine, and Sildenafil-Treated Rat Models: An Experimental Study


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Altintop I., Tatlı M., Karakukcu C., Sarica Z., Yay A. H., Balcıoğlu E., ...Daha Fazla

MEDICINA-LITHUANIA, cilt.54, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 54
  • Basım Tarihi: 2018
  • Doi Numarası: 10.3390/medicina54040054
  • Dergi Adı: MEDICINA-LITHUANIA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: contrast-induced nephropathy, hypoxia-inducible factor 2, N-acetyl-cysteine, sildenafil, CONTRAST-INDUCED NEPHROPATHY, RISK, HIF-2-ALPHA, ACTIVATION
  • Erciyes Üniversitesi Adresli: Evet

Özet

Background and Objectives: Contrast-induced nephropathy (CIN), is acute renal damage due to contrast agents. This study is conducted to evaluate serum and renal heterodimeric nuclear transcription factor (HIF)-2 alpha levels and its tissue expression in contrast-induced nephropathy, and in N-acetyl cysteine (NAC)-and Sildenafil-treated rat models. Materials/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN + NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modeling, prophylactic treatment was performed at the 24th and 48th h. After 48 h of modeling, blood, urine, and tissue samples were obtained for biochemical analyses. HIF-2-alpha levels were measured in renal tissue, serum, and urine samples. Renal sections were also performed for histopathologic and immunohistochemical evaluations of renal injury and HIF-2-alpha expression. Results: In the CIN model, HIF-2 alpha levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC efficiently decreased renal damage due to contrast agents, as shown in histopathologic examinations (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2 alpha levels were significantly decreased (p < 0.05). Conclusions: The current study shows that serum and tissue HIF-2 alpha levels decrease in CIN. Besides, the levels and tissue expression of HIF-2 alpha decrease with both NAC and sildenafil treatments. With further studies, HIF-2 alpha can be investigated as a biomarker of CIN and can be used in the follow-up of patients with CIN.