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 RESEARCH ARTICLE
Year : 2014  |  Volume : 46  |  Issue : 3  |  Page : 309-315

Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations


Division of Pharmacology, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India

Correspondence Address:
Anil Kumar
Division of Pharmacology, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh
India
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Source of Support: Authors gratefully acknowledge the fi nancial support of UGC (University Grants Commission), New Delhi to carry out the research work., Conflict of Interest: None


DOI: 10.4103/0253-7613.132180

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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.






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