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

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). Conclusion: 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.