The Effects of the Phosphodiesterase-5 Inhibitor Sildenafil on Neuroinflammation and Cell Viability Against Aluminum Chloride-Induced Neurotoxicity

28. Ulusal 3. Uluslararası Farmakoloji Kongresi, Antalya, Türkiye, 20 - 23 Kasım 2025, ss.109-110, (Özet Bildiri)

Objective: Aluminum chloride (AlCl3) is known to cross the blood–brain barrier, increase oxidative

stress, impair neurogenesis, and trigger tau protein aggregation, thereby accelerating the

pathogenesis of Alzheimer’s disease. These effects have been linked to deterioration in learning,

memory, and other cognitive functions. In parallel, the phosphodiesterase-5 (PDE-5) inhibitor

sildenafil prevents cGMP degradation and activates the NO/cGMP/PKG/CREB signaling pathway,

supporting cerebral vasodilation, enhancing synaptic plasticity and neurogenesis, and reducing

oxidative stress and neuroinflammation. Based on these properties, sildenafil has been suggested

to possess potential neuroprotective effects. The aim of this study was to investigate the protective

role of sildenafil against AlCl3-induced neurotoxicity, which is of growing concern due to the

widespread industrial use and biological toxicity of AlCl3.

Methods: SH-SY5Y cells were cultured under appropriate conditions and treated with different

concentrations of AlCl3 and sildenafil. Following 24 hours of incubation, cell viability was assessed

using the MTT assay to determine the optimal concentrations. Based on these findings, the

neuroprotective effects of sildenafil (0.0016, 0.008, and 0.04 μM) against AlCl3-induced (300 μM)

neurotoxicity were examined in three experimental designs: pre-treatment, co-treatment, and post-

treatment. Cell viability was compared across groups, and in conditions where neuroprotection

was observed, inflammatory markers (IL-1β, IL-6, TNF-α, and IL-8) were quantified using ELISA.

Results: Exposure to AlCl3 (300 μM) significantly reduced SH-SY5Y cell viability and increased

the levels of IL-1β, IL-6, TNF-α, and IL-8. Sildenafil, particularly in pre-treatment groups (0.0016,

0.008, and 0.04 μM), enhanced cell survival and showed clear neuroprotective effects.

Furthermore, sildenafil at 0.008 and 0.04 mM significantly attenuated AlCl3-induced cytokine

elevations.

Conclusion: Sildenafil showed protective effects against AlCl3-induced neurotoxicity, likely

through preservation of cell viability and suppression of inflammatory responses. These findings

support its potential as a neuroprotective agent in AlCl3-related models.