Adropin ameliorates behavioral seizures and the relevant neuroinflammation, oxidative stress, and neural damage in a rat model of pentylenetetrazole-induced seizure potentially by reducing the activation of NF-κB/IkB-α signaling pathway

This study aimed to investigate the effects of adropin on seizure activity, neuroinflammation, oxidative stress, and cognitive function in a rat model of pentylenetetrazole (PTZ)-induced seizure. Male Wistar rats were randomly assigned to six groups (n = 7/each group), as follows: control, PTZ, adropin (2 µg/kg or 10 µg/kg) + PTZ, L-NAME + adropin + PTZ, and valproic acid + PTZ groups. Anticonvulsant medicine valproic acid was administered as positive control. Non-selective nitric oxide synthase inhibitor L-NAME was administered together with adropin to elucidate whether adropin exerts its possible effects through the nitric oxide pathway. Behavioral epileptic seizures, biochemical markers of neuroinflammation and relevant pathway, oxidative stress, cognitive function and neural survival/damage were assessed. Adropin (10 µg/kg) reduced PTZ-induced seizure severity and duration, and mitigated cortical and hippocampal pro-inflammatory (IL-1β, IL-6, TNF-α and related transcription factors pNF-κB-p65 and pIκBα), oxidant (MDA) and neural damage (GFAP) markers while elevating anti-inflammatory (IL-10), antioxidant (SOD) and neural survival (BDNF) markers. Combining adropin and L-NAME also exhibited similar effects to adropin alone. In other words, blocking systemic nitric oxide production did not alter the effects of adropin. However, adropin did not significantly improve cognitive performance in the passive avoidance test. Valproic acid, as a positive control, reversed the PTZ-induced effects. These findings suggest that adropin exhibits anticonvulsant, anti-inflammatory, antioxidant and neuroprotective properties in PTZ-induced seizure model potentially through modulation of NF-κB/IkB-α signalling. Therefore, adropin may be a multi-faceted and promising agent in the prevention and management of epileptic seizures in the future.