Preventive effect of melatonin against brain mitochondria DNA damage, lipid peroxidation and seizures induced by kainic acid

被引:64
作者
Mohanan, PV [1 ]
Yamamoto, H [1 ]
机构
[1] Univ Tsukuba, Inst Community Med, Tsukuba, Ibaraki 3058575, Japan
基金
日本学术振兴会;
关键词
melatonin; kainic acid; mitochondria DNA; hydroxyl radical; lipid peroxidation;
D O I
10.1016/S0378-4274(01)00475-1
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The effects of kainic acid on mitochondria DNA (mtDNA) or lipid peroxidation in mice brain and, preventive effects of metatonin against its effects were investigated in vivo, Broad-spectrum limbic and severe sustained seizures were observed in all mice when kainic acid (45 mg/kg) was injected intraperitoneally (ip) to eight mice. These seizures were completely abolished by the simultaneous administration of melatonin (20 mg/kg, ip), a potent scavenger of hydroxyl radical. However. slight limbic seizures or severe sustained seizures were observed when melatonin was injected in animals 30 min before or 15 min after the kainic acid administration. The administration of kainic acid caused damage to mtDNA in brain frontal and middle cortex. These effects were abolished when melatonin was injected in animals 0 or 30 min before, but not 15 min after the kainic acid administration, In vitro or in vivo exposure of kainic acid elicited an increase in lipid peroxidation in a concentration- or dose-dependent manner. The increased lipid peroxidation induced by kainic acid was attenuated by co-treatment with melatonin. These results indicate that there may be a positive relationship among seizures, brain mtDNA damages and increased lipid peroxidation. Hence, our present results suggest that the hydroxyl radicals produced by kainic acid cause damage on mtDNA and the increase of lipid peroxidation in brain, leading to severe seizures. These effects were completely prevented by co-treatment with melatonin, a potent scavenger of hydroxyl radicals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:99 / 105
页数:7
相关论文
共 27 条
[2]   OXIDATIVE STRESS, GLUTAMATE, AND NEURODEGENERATIVE DISORDERS [J].
COYLE, JT ;
PUTTFARCKEN, P .
SCIENCE, 1993, 262 (5134) :689-695
[3]  
Cui JK, 2000, FASEB J, V14, P955
[4]   A COMPARISON OF FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE [J].
DUARA, R ;
LOPEZALBEROLA, RF ;
BARKER, WW ;
LOEWENSTEIN, DA ;
ZATINSKY, M ;
EISDORFER, CE ;
WEINBERG, GB .
NEUROLOGY, 1993, 43 (07) :1377-1384
[5]   Increased risk of dementia in mothers of Alzheimer's disease cases: Evidence for maternal inheritance [J].
Edland, SD ;
Silverman, JM ;
Peskind, ER ;
Tsuang, D ;
Wijsman, E ;
Morris, JC .
NEUROLOGY, 1996, 47 (01) :254-256
[6]   Mitochondrial disease in mouse results in increased oxidative stress [J].
Esposito, LA ;
Melov, S ;
Panov, A ;
Cottrell, BA ;
Wallace, DC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) :4820-4825
[7]   Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy [J].
Hellier, JL ;
Patrylo, PR ;
Buckmaster, PS ;
Dudek, FE .
EPILEPSY RESEARCH, 1998, 31 (01) :73-84
[8]   Spontaneous motor seizures of rats with kainate-induced epilepsy: effect of time of day and activity state [J].
Hellier, JL ;
Dudek, FE .
EPILEPSY RESEARCH, 1999, 35 (01) :47-57
[9]   Human brain contains high levels of heteroplasmy in the noncoding regions of mitochondrial DNA [J].
Jazin, EE ;
Cavelier, L ;
Eriksson, I ;
Oreland, L ;
Gyllensten, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (22) :12382-12387
[10]  
JOHNS DR, 1995, NEW ENGL J MED, V333, P638, DOI 10.1056/NEJM199509073331007