Scholarlink

Background <p>Epilepsy 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.</p> Methods <p>Swiss albino mice (<i>n</i> = 9/group) were divided into seven groups and treated with PFD 100, 200, 300&#xa0;mg/kg orally and PTZ (25&#xa0;mg/kg intraperitoneally) at alternate days. Sodium Valproate (200&#xa0;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 <i>via</i> histopathological changes.</p> Results <p>PFD significantly reduced seizure severity dose-dependently, with 300&#xa0;mg/kg demonstrating the greatest effect (<i>p</i> &lt; 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) (<i>p</i> &lt; 0.001). Histology confirmed reduced cardiac fibrosis, especially at 300&#xa0;mg/kg dose of PFD.</p> Conclusion <p>Pirfenidone exhibits cardioprotective, antioxidant and anti-inflammatory actions in seizure-associated cardiac injury <i>via</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2026年1月7日

查看全文
  • Mansi Dahalia,
  • Haya Majid,
  • Divya Vohora,
  • Nidhi

摘要

Background

Epilepsy 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.

Methods

Swiss 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.

Results

PFD 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.

Conclusion

Pirfenidone 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.