Immunomodulatory effects of interleukin-4 in neurological disorders induced by K+ channel blocker

Ahras-Sifi, N.; Ladjel-Mendil, Amina; Martin‐Eauclaire, Marie‐France; Laraba-Djebari, Fatima

doi:10.1016/j.jns.2019.10.428

Cited by 1 publication

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“…Interestingly, no study detected the targeted effect of COQ10 on hippocampal ferroptosis in a SE rat model. However, there was a different study on the neuroprotective effect of COQ10 in epileptic models in rodents (Ahras-sifi and Laraba-djebari 2020 ; Bhardwaj and Kumar 2016 ; Mao et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

CoQ10 targeted hippocampal ferroptosis in a status epilepticus rat model

Fikry,

Saleh,

Mahmoud

et al. 2024

Cell Tissue Res

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Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

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Section: Discussionmentioning

confidence: 99%