Cerebral protective effect and radical scavenging action.
The role of radical scavenging action in cerebral protective effect of drugs was investigated in vitro. Incubation of rat brain mitochondrial suspension with ascorbic acid and Fe2+ resulted in the formation of malondialdehyde and a decrease in the turbidity of the suspension, indicating that the mitochondria were peroxidatively disintegrated. Nizofenone at 10 micro M or more inhibited the peroxidative disintegration of mitochondria, and complete inhibition was observed at 100-200 micro M. The action of nizofenone was also ascertained by experiments with rat liver mitochondria. The anti-peroxidative activity of nizofenone was estimated to be approximately equivalent to that of alpha-tocopherol, and this property was unique. Among the cerebral protective drugs tested, thiopental was only slightly efficient, and pentobarbital, phenobarbital, and dimethyl sulfoxide had no effect. In addition, nizofenone was found to scavenge a stable free radical, diphenyl-p-picrylhydrazyl, but the barbiturates did not. These findings suggest that there is no intimate relationship between cerebral protective effect and free radical scavenging action.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001713:Biphenyl Compounds; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006834:Hydrazines / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007202:Indicators and Reagents / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010851:Picrates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001713:Biphenyl Compounds; D006834:Hydrazines; D007093:Imidazoles; D007202:Indicators and Reagents; D008054:Lipid Peroxides; D010851:Picrates; C016910:nizofenone; C004931:1,1-diphenyl-2-picrylhydrazyl; D010424:Pentobarbital; D001205:Ascorbic Acid; D004121:Dimethyl Sulfoxide; D010634:Phenobarbital