The potential antiepileptic activity of astaxanthin in epileptic rats treated with valproic acid

• Published in: Saudi pharmaceutical journal Vol. 29; no. 5; pp. 418 - 426
• Main Authors: Ata Yaseen Abdulqader, Yussra, Abdel Kawy, Hala Salah, Mohammed Alkreathy, Huda, Abdullah Rajeh, Nisreen
• Format: Journal Article
• Language: English
• Published: Saudi Arabia Elsevier B.V 01.05.2021; Elsevier
• Subjects: Astaxanthin; Epilepsy; Original; Pentylenetetrazol; ROS; Valproic acid; AED; ASTA; NO; OPA; BBB; Epilepsy; Astaxanthin; Pentylenetetrazol; VPA; CNS; MDA; Valproic acid; GFAP; PC; TNF-α; ROS; PTZ; GTCS; GSH; HPLC; MDA, Malondialdehyde; ASTA, Astaxanthin; TNF-α, Tumor necrosis factor-α; OPA, o-Phthalaldehyde; NO, Nitrous oxide; GTCS, Generalized tonic-clonic seizure; BBB, Blood brain barrier; GFAP, Glial fibrillary acidic protein; GSH, Reduced glutathione; PTZ, Pentylenetetrazol; ROS, Reactive oxygen species; VPA, Valproic acid; AED, Antiepileptic drugs; CNS, Central nervous system; PC, Protein carbonyl; HPLC, High performance liquid chromatography
• ISSN: 1319-0164; 2213-7475
• DOI: 10.1016/j.jsps.2021.04.002

Epilepsy is a neurological disease characterized by sudden, abnormal, and hyper- discharges in the central nervous system (CNS). Valproic acid (VPA) is commonly used as a broad-spectrum antiepileptic therapeutic. However, in many cases, patients develop resistance to VPA treatment due to overwhelming oxidative stress, which in turn might be a major catalyst for disease progression. Therefore, antioxidants can potentially become therapeutic agents by counteracting reactive oxygen species (ROS)-mediated damage. The present study is aimed to evaluate the potential antiepileptic effect of astaxanthin (ASTA) in pentylenetetrazol (PTZ) induced epileptic model rats that are chronically treated with VPA for 8 weeks. Fifty-male Wistar rats were randomly divided into five groups: Non-PTZ group, PTZ, PTZ/VPA, PTZ/ASTA, and PTZ/VPA/ASTA treated groups. PTZ/VPA treated group showed a neuroprotective effect with improvement in antioxidant levels, behavioral test, and histopathological changes induced by PTZ. VPA also exhibited an anti-inflammatory effect as its treatment resulted in the reduction of tumor necrosis factor-α (TNF-α). ASTA exhibited an anticonvulsant effect and enhanced anti-inflammatory effect as compared to VPA. During the combined therapy, ASTA potentiated the antiepileptic effect of the VPA by reducing the oxidative stress and TNF-α as well as increased the glutathione (GSH) levels. Also, there were substantial improvements in the behavioral and histopathological changes in the VPA/ASTA treated group as compared to the VPA treated group. ASTA could have an antiepileptic and anti-inflammatory effect by reducing ROS generation. Therefore, co-administration of both the therapeutics (VPA/ASTA) has a synergistic effect in treating epilepsy and could potentially minimize recurrence and/or exacerbation of seizures.