Association of Pirfenidone and its Cardioprotective effects in Pentylenetetrazole-induced kindling model of Epilepsy through the High mobility group Box-1/Toll-Like Receptor-4 pathway.

backgroundEpilepsy and cardiac dysfunction are increasingly recognized as interrelated conditions, with chronic epilepsy contributing to systemic inflammation, oxidative stress, and autonomic dysregulation, adversely impacting cardiovascular health. However, current treatments seldom address both neurological and cardiovascular complications simultaneously. This study evaluates the potential of Pirfenidone (PFD), an antifibrotic and anti-inflammatory agent, to reduce cardiac inflammation, oxidative stress, and fibrosis in an epilepsy model using Pentylenetetrazole (PTZ)-induced kindling.

methodsSwiss albino mice (n = 9/group) were divided into seven groups and treated with PFD 100, 200, 300 mg/kg orally and PTZ (25 mg/kg intraperitoneally) at alternate days. Sodium Valproate (200 mg/kg orally) was used as a standard. Seizure activity was monitored, and cardiac tissue was analyzed for markers of oxidative stress, inflammatory cytokines, and fibrosis via histopathological changes.

resultsPFD significantly reduced seizure severity dose-dependently, with 300 mg/kg demonstrating the greatest effect (p < 0.05). Cardiac oxidative stress markers Superoxide Dismutase, Malondialdehyde, Reduced Glutathione and catalase improved significantly. Inflammatory markers were also markedly reduced, including High Mobility Group Box-1 (HMGB1) and Toll-Like Receptor-4 (TLR4) (p < 0.001). Histology confirmed reduced cardiac fibrosis, especially at 300 mg/kg dose of PFD.

conclusionPirfenidone exhibits cardioprotective, antioxidant and anti-inflammatory actions in seizure-associated cardiac injury via HMGB1/TLR4 pathway modulation. These findings suggest its potential as an adjunctive therapy in epilepsy patients at risk of cardiovascular complications. Further clinical studies are warranted.