Neuroprotective mechanisms of sildenafil and selenium in PTZ‐kindling model: Implications in epilepsy
Abstract
Abstract Epilepsy is one of the furthermost common neurodegenerative diseases affecting above 50 million individuals worldwide. The pathogenesis of epileptic seizures is not satisfactorily explored, and hence more effective anti‐convulsive therapies are indispensable. Current study aimed to investigate the mechanisms of the potential neuroprotective effects of sildenafil/selenium on chemically‐induced convulsions in mice. Kindling model was induced using pentylenetetrazol (PTZ; 35 mg/Kg, 11 doses, intraperitoneally, every other day). PTZ‐insulted groups were treated intraperitoneally with sildenafil (20 mg/Kg), selenium (0.2 mg/Kg) or their combination; 30 min before PTZ administration. PTZ‐kindled model showed a significant loss of neuronal cells concurrently with nitrative/oxidative stress and lipid peroxidation. This was associated with enhanced expression of inducible nitric oxide synthase (iNOS), hemeoxygenase‐1 (HO‐1) and vascular endothelial growth factor (VEGF) along with increased activity of thioredoxin reductase (TrxR) in hippocampal tissue. Individual treatment with sildenafil or selenium showed partial neuroprotection, simultaneously with lower hippocampal expression of 4‐hydroneonenal (4‐HNE), nitrotyrosine, iNOS and HO‐1, yet without reaching normal levels. Sildenafil, but not selenium, enhanced the expression of VEGF and the endothelial cell marker CD34. The joint treatment with sildenafil and selenium preserved hippocampal neuronal count, improved kindling…
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