title: Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Hesp possesses potent anticonvulsant activity which might be mediated through modulation of gamma-amino butyric acid/benzodiazepine receptor action.
authors.affiliation: Division of Pharmacology, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Division of Pharmacology, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
authors.forename: Sree
authors.initials: S
authors.lastname: Lalitha
authors.affiliation: Division of Pharmacology, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
authors.forename: Jitendriya
authors.initials: J
authors.lastname: Mishra
mesh_terms: D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D003576:Electron Transport Complex IV / Q000378:metabolism; D000077206:Gabapentin; D005978:Glutathione / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010433:Pentylenetetrazole; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D006569:Hesperidin; D002374:Catalase; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D005978:Glutathione; D003975:Diazepam; D010433:Pentylenetetrazole
keywords: Mitochondrial dysfunction; myoclonic jerks; oxidative stress; seizure