EPC-K1, a hydroxyl radical scavenger, prevents 6-hydroxydopamine-induced dopamine depletion in the mouse striatum by up-regulation of catalase activity.
We examined the effect of pretreatment with EPC-K1, a potent hydroxyl radical scavenger, on 6-hydroxydopamine (6-OHDA)-induced reduction of dopamine (DA) and its metabolites in the mouse striatum. EPC-K1 was mixed with diet (0.2%, wt/wt) for 1 or 2 weeks, and then 6-OHDA (60 microg in 2 microl of saline solution) was injected intracereberoventricularly. Mice continued to be fed EPC-K1-containing diet for another one week before they were sacrificed. The concentrations of DA and its metabolites in the striatum were measured by high performance liquid chromatography. 6-OHDA reduced the level of DA and its metabolites in the striatum. Pretreatment with EPC-K1 for 2 weeks, but not for 1 week, abrogated the neurotoxic effect of 6-OHDA on striatal concentrations of DA and its metabolites. Measurement of striatal concentrations of thiobarbituric acid reactive substances, glutathione, and malonaldehyde plus 4-hydroxynonenal, and the activities of superoxide dismutase and catalase in EPC-K1 treated mice showed an increase in catalase activity after 2 weeks of such treatment. No other changes in anti-oxidants levels were noted. Our results suggest that EPC-K1 counteracts the neurotoxicity of 6-OHDA by increasing catalase activities.
Kabuto
H
H
Department of Medical Technology, Kagawa Prefectural College of Health Sciences, Kida-gun, Japan. kabuto@chs.pref.kagawa.jp
Yokoi
I
I
Iwata-Ichikawa
E
E
Ogawa
N
N
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D017665:Hydroxyl Radical; D007276:Injections, Intraventricular; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; D015102:3,4-Dihydroxyphenylacetic Acid; D014810:Vitamin E; D017665:Hydroxyl Radical; D008315:Malondialdehyde; C066638:potassium ascorbyl tocopheryl phosphate; D016627:Oxidopamine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine; D006719:Homovanillic Acid