Protective effect of a novel free radical scavenger, OPC-14117, on wobbler mouse motor neuron disease.
A possible protective effect of a novel free radical scavenger, OPC-14117, on the progressive motor neuron death in wobbler mice was examined. Clinical parameters such as mortality, body weight, motor activity as a rolling number of circular cage, and forelimb muscle power as grasping on a rolling column, an angle of slipping down from slope, and hanging ability on a flat plate were compared every 4 weeks from 4 to 36 weeks of age among mice groups treated with vehicle or daily oral administration of OPC-14117 of 10 or 30 mg/kg body weight. The treatment with OPC-14117 dose dependently improved the clinical parameters such as mortality, motor activity, and forelimb weakness. Pathological analysis showed that a diffuse neurogenic change in the forelimb muscle was improved at 36 weeks of age in the drug treated mice with a marked preservation of motor neurons in the spinal cord. Treatment of the mice with the drug reduced age-dependent increase of lipid peroxides in the spinal cord in vivo, and a supplement of the drug to the homogenate of spinal cord in vitro ameliorated the formations of lipid peroxides generated by an exogenous addition of ascorbate or xanthine/xanthine oxidase. These results suggest that OPC-14117 has a protective effect on the motor neuron death probably as a free radical scavenger, resulting in an improvement of clinical symptoms in wobbler mice.
Abe
K
K
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Morita
S
S
Kikuchi
T
T
Itoyama
Y
Y
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006579:Heterozygote; D006720:Homozygote; D007189:Indans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D016019:Survival Analysis
D000447:Aldehydes; D003432:Cross-Linking Reagents; D016166:Free Radical Scavengers; D007189:Indans; D018696:Neuroprotective Agents; D010879:Piperazines; D008315:Malondialdehyde; C074852:OPC 14117; C027576:4-hydroxy-2-nonenal