Evaluation of the Neuroprotective Effect of Diosmin in Posttraumatic Epilepsy-Induced Oxidative Stress in Mice Brains

ABSTRACT Background: Oxidative stress plays a crucial role in the pathogenesis and progression of posttraumatic epilepsy (PTE), leading to neuronal damage and epileptic foci formation. Diosmin, a flavonoid with potent antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent to counteract oxidative damage in neurodegenerative conditions. This study aimed to investigate the neuroprotective effects of diosmin on oxidative stress markers and antioxidant enzyme activities in a mice model of PTE. Method: Adult female mice were used to establish a post-traumatic epilepsy (PTE) model through traumatic brain injury, inducing oxidative stress. Mice were randomly divided into seven groups (n=9): saline control, SPS + saline, PTZ (37.5 g/kg, i.p.) + saline, SPS + PTZ, PTZ + diosmin (25 mg/kg, p.o.), SPS + PTZ + diosmin (50 mg/kg, p.o.), and SPS + PTZ + diazepam (10 mg/kg, p.o.). Seizures were induced in groups 3-7 with PTZ administered every other day from PTSD days 8 to 21, with treatments given daily for 14 days. Oxidative stress markers, including malondialdehyde (MDA), and antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT), were measured in the prefrontal cortex (PFC) and hippocampus (HC). Results: Diosmin administration significantly reduced MDA concentrations in both the PFC and HC, indicating a decrease in lipid peroxidation and oxidative damage. Additionally, diosmin enhanced the activities of SOD and CAT enzymes, suggesting an improvement in the brain's antioxidant defenses. These effects were particularly pronounced in brain regions critical for cognitive and emotional functions, highlighting diosmin's potential in mitigating oxidative stress-related neuronal damage. Conclusion: The findings from this study suggest that diosmin exhibits strong neuroprotective properties by reducing oxidative stress and enhancing antioxidant defenses in a mice model of PTE. This dual action of diosmin underscores its potential as a therapeutic agent for managing PTE and possibly other neurodegenerative disorders associated with oxidative stress. Keywords: Posttraumatic epilepsy; Oxidative stress; Neuroprotection; Antioxidant enzymes; Diosmin