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

Abstract

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-α 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-α expression. Results: In the CIN model, HIF-2α 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-2α levels were significantly decreased (p < 0.05). Conclusions: The current study shows that serum and tissue HIF-2α levels decrease in CIN. Besides, the levels and tissue expression of HIF-2α decrease with both NAC and sildenafil treatments. With further studies, HIF-2α can be investigated as a biomarker of CIN and can be used in the follow-up of patients with CIN.

Exploring the Multifaceted Potential of Sildenafil in Medicine

“…Iohexol-induced nephropathy Wistar female rats 50 mg/kg bw, orally Reduced serum and renal tissue levels of HIF-2α and sCr [184].…”

Renoprotective Effect of Vardenafil and Avanafil in Contrast-Induced Nephropathy: Emerging Evidence from an Animal Model

“…Both sildenafil and tadalafil have been reported to lower sCr levels, demonstrating a positive effect against CIN [ 17 , 21 , 40 , 41 , 42 ]. Evidence from previous studies has indicated that KIM-1 has shown a renoprotective effect mainly in AKI, measured in urine or in renal tissue [ 28 ].…”

“…Finally, there is evidence that CM induces significant histological alterations at the organ/tissue level. Histological alterations include increased organ weight and Bowman space, lobulated glomerulus, alterations of the macula densa region [ 22 ], medullary congestion [ 40 ], inflammatory cell infiltration, intratubular cast formation and obstruction, tubular vacuolization/degeneration-necrosis [ 17 , 41 ], and hemorrhagic changes within the kidney [ 22 ]. Most of the available evidence sources denote an attenuation of the effect of CM following PDE5I administration [ 28 ].…”

“…As a result, NAC is still commonly used in daily clinical practice as previously described [ 10 ]. Last but not least, promising results have been reported in several animal studies using NAC as either the main treatment under investigation or standard/conventional treatment (positive control) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Apart from its antioxidant properties [ 23 ], supporting biological plausibility of efficacy relies on its vasodilatory effects [ 24 ], namely its ability to cause renal artery vasodilatation/renal blood flow increase, improving renal hemodynamics [ 10 ].…”