Tauroursodeoxycholic Acid Exerts Neuroprotective Effects in Epilepsy via Suppression of Ferroptosis

Epilepsy is a complex neurological disorder marked by recurrent, unprovoked seizures. Ferroptosis is characterized by the accumulation of oxidative stress and is associated with the occurrence and development of epilepsy. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has demonstrated neuroprotective properties in various neurodegenerative conditions. In this study, we examined the antiepileptic efficacy of TUDCA and sought to elucidate its underlying mechanisms of action.

The antiepileptic effects of TUDCA were evaluated using electroencephalogram recordings, behavioral testing, and immunohistochemistry in a Lithium chloride (LiCl)- Pilocarpine (Pilo)-induced epilepsy rat model, alongside a glutamate-induced neuronal cell model. Neuronal ferroptosis was assessed through western blotting and immunofluorescence.

In vivo, TUDCA significantly alleviated both seizure severity and neuronal damage by inhibiting oxidative stress and ferroptosis. In vitro, TUDCA similarly exerted neuroprotective effects and effectively suppressed neuronal ferroptosis.

TUDCA mitigates epilepsy through the suppression of ferroptosis, suggesting its potential as a therapeutic agent for epilepsy treatment.