AIM: Epilepsy is a chronic neurological disorder with complex pathophysiology. 
Several evidences suggest a role of oxidative stress and mitochondrial 
dysfunction in pathophysiology of epilepsy. Hesperidin (Hesp) acts as a powerful 
anti-oxidant agent against superoxide, singlet oxygen, and hydroxyl radicals. 
Thus, this study was undertaken to evaluate the possible neuroprotective 
mechanism of Hesp against pentylenetetrazole (PTZ)-induced convulsions in mice.
MATERIALS AND METHODS: Sixty males Laca mice (20-25 g) were randomly divided 
into 10 treatment groups (n = 6). Seven days pretreatment of Hesp (100, 200 
mg/kg, p.o.) was carried out before PTZ (80 mg/kg, intraperitoneal [i.p.]) 
challenge, whereas diazepam (DZP) (0.2, 0.5 mg/kg) and gabapentin (Gbp) (10, 20 
mg/kg) were administered i.p. 30 min before PTZ administration, that is, on 
7(th) day. Following PTZ challenge, severity of convulsions (onset of jerks, 
myoclonic seizures, extensor phase and death), brain anti-oxidant enzyme levels 
and mitochondrial complex enzymes activities were estimated.
RESULTS: Single i.p. PTZ (80 mg/kg) challenge demonstrated severe convulsions, 
oxidative damage (raised lipid peroxidation [LPO], nitrite concentration as well 
as depleted reduced glutathione, superoxide dismutase and catalase levels), and 
depletion of mitochondrial enzyme Complex (I, II, IV) activities. Hesp (200 
mg/kg), DZP (0.5 mg/kg) and Gbp (20 mg/kg) pretreatments attenuated PTZ induced 
behavioral, biochemical and mitochondrial alterations. However, administration 
of Hesp (100 mg/kg) in combination with DZP (0.2 mg/kg) or Gbp (10 mg/kg) 
potentiated their neuroprotective effect, which was significant as compared to 
their effects in PTZ treated animals.
CONCLUSION: Hesp possesses potent anticonvulsant activity which might be 
mediated through modulation of gamma-amino butyric acid/benzodiazepine receptor 
action.