Investigation of Contrast-Induced Neurotoxicity and the Effects of Sildenafil and N-Acetylcysteine on HIF-1α Levels in Wistar Rats

Altintop I., Tatli M., Sarica Z. S., YAY A. H., KARAKÜKCÜ Ç.

Brain Sciences, cilt.16, sa.4, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 4
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3390/brainsci16040362
  • Dergi Adı: Brain Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Psycinfo, Directory of Open Access Journals
  • Anahtar Kelimeler: contrast media-induced encephalopathy, neuroprotection, oxidative stress, phosphodiesterase-5 inhibitors
  • Erciyes Üniversitesi Adresli: Evet

Özet

Background: Contrast-induced encephalopathy (CIE) is an uncommon yet clinically significant complication associated with iodinated contrast media, with its mechanisms remaining unclear. Objective: The aims of this study are to examine the neurotoxic effects of contrast media and assess the neuroprotective roles of N-Acetylcysteine (NAC) and sildenafil with regard to HIF-1α expression. Methods: Thirty-six female Wistar albino rats (n = 36) were allocated into four experimental groups (n = 9 each): control, contrast media + saline (CMA + Saline), contrast media + NAC (CMA + NAC), and contrast media + sildenafil (CMA + Sildenafil). NAC (150 mg/kg) and sildenafil (50 mg/kg/day) were administered intragastrically for 48 h before exposure to contrast media. Biochemical, histopathological, and immunohistochemical evaluations were conducted 48 h post-contrast administration. Results: Exposure to contrast media resulted in neuronal death, vascular obstruction, and increased hypoxia-inducible factor-1 alpha (HIF-1α) immunoreactivity. The primary outcome measure, tissue HIF-1α concentration by ELISA, did not differ significantly among groups (p = 0.119). Semi-quantitative immunohistochemical analysis revealed significant group differences in HIF-1α immunoreactivity (p < 0.001), with all injury/treatment groups differing significantly from control. The difference between the contrast media group and the sildenafil-treated group approached but did not reach statistical significance after correction for multiple comparisons (Dunn’s test, p = 0.050). Conclusions: The primary biochemical endpoint did not demonstrate significant group differences. Secondary IHC analysis suggests a potential attenuation of HIF-1α immunoreactivity by sildenafil, though this did not reach statistical significance and requires confirmation in adequately powered studies. HIF-1α immunoreactivity warrants further investigation as a potential biomarker for contrast-induced neural injury.