title: Effects of midazolam and phenobarbital on brain oxidative reactions induced by pentylenetetrazole in a convulsion model.
abstract: BACKGROUND
  Brain oxidative reactions are involved in epilepsy as well as neurodegenerative diseases. In animal convulsion models, some anticonvulsants have been found to suppress oxidative reactions associated with convulsions. However, the effect of anticonvulsants on brain oxidative reactions has not fully been clarified.
  
  
  OBJECTIVE
  Midazolam and phenobarbital are often used as an intravenous anesthetic, and are known to have anticonvulsive effect, but antioxidative effect of these drugs has rarely been studied. Thus, the purpose of this study was to evaluate the effects of these drugs on the degree of convulsions and brain oxidative reactions in an animal convulsion model.
  
  
  METHODS
  In order to evaluate brain oxidative reactions, we measured malondialdehyde (MDA) level and heme oxygenase (HO)-1 mRNA expression level in the brain of mice in a convulsion model generated by a single injection of pentylenetetrazole (PTZ). We evaluated the effects of midazolam and phenobarbital on the degree of PTZ-induced convulsions and on the changes in brain MDA level and HO-1 mRNA expression level.
  
  
  RESULTS
  After PTZ injection, severe convulsions were observed in all mice. MDA level was increased in the whole brain, while HO-1 mRNA expression level was increased only in the hippocampus. Both midazolam and phenobarbital prevented the convulsions and suppressed the increase in both MDA level and HO-1 mRNA expression level in the brain.
  
  
  CONCLUSIONS
  In this study, both midazolam and phenobarbital suppressed PTZ-induced MDA and HO-1 reactions in the brain, suggesting that these drugs inhibit brain oxidative reactions in a convulsion model.
authors.affiliation: Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Arai
authors.forename: Shigeru
authors.initials: S
authors.lastname: Maeda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Higuchi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tomoyasu
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shimada
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008874:Midazolam / Q000494:pharmacology* / Q000627:therapeutic use; D010084:Oxidation-Reduction / Q000187:drug effects; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D008874:Midazolam; D010433:Pentylenetetrazole; D010634:Phenobarbital