Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy.
Intracortical injection of iron ions has been used as a model of posttraumatic epilepsy. Oxidation of lipids in neural membranes by reactive oxygen species, especially hydroxyl radicals (OH), is involved in the mechanisms responsible for iron-induced seizures. We examined the scavenging effects of adenosine (Ado) and 2-chloroadenosine (Cl-Ado) on OH radicals and superoxide (O2.-) using an electron spin resonance (ESR) spectrometer, and the occurrence of epileptic discharges in electrocorticogram (ECoG) induced by FeCl3 injection into the sensorimotor cortex of rats. Though DMPO-O2.- spin adducts generated by the hypoxanthine-xanthine oxidase system were not quenched by Ado or Cl-Ado, 5 mM of each showed a quenching effect on DMPO-OH spin adducts (5.3 x 10(16) spins/ml) generated by the Fenton reagent. In ECoG of rats, spike discharges appeared 15-45 min after FeCl3 injection (500 nmol) into the sensorimotor cortex, and polyspikes and/or ictal patterns were observed 70-90 min after the injection. Cl-Ado (1 mg/kg) or Ado (5 mg/kg) injected intraperitoneally 30 min prior to the FeCl3 injection suppressed or delayed the occurrence of epileptic discharges induced by FeCl3. Cl-Ado and Ado may suppress the occurrence of epileptic discharges by scavenging OH and by their anticonvulsant effect.
Yokoi
I
I
Department of Neuroscience, Okayama University Medical School, Japan.
Toma
J
J
Liu
J
J
Kabuto
H
H
Mori
A
A
D015762:2-Chloroadenosine / Q000494:pharmacology / Q000627:therapeutic use*; D000241:Adenosine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002712:Chlorides; D003497:Cyclic N-Oxides; D004569:Electroencephalography; D004578:Electron Spin Resonance Spectroscopy; D004834:Epilepsy, Post-Traumatic / Q000139:chemically induced / Q000517:prevention & control*; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D017665:Hydroxyl Radical / Q000378:metabolism*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D002712:Chlorides; D003497:Cyclic N-Oxides; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D007042:Hypoxanthines; D013113:Spin Labels; D013481:Superoxides; D015762:2-Chloroadenosine; D019271:Hypoxanthine; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D014969:Xanthine Oxidase; D000241:Adenosine; C024555:ferric chloride