期刊
FUNDAMENTAL & CLINICAL PHARMACOLOGY
卷 35, 期 2, 页码 351-363出版社
WILEY
DOI: 10.1111/fcp.12598
关键词
lacosamide; kindling; pentylenetetrazole; oxidative stress; comet assay; neuroinflammation
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [307064/2013-1]
- Federal University of Rio Grande do Sul (UFRGS) [34134]
This study evaluated the effects of lacosamide on biochemical and mitochondrial parameters after PTZ kindling in mice. Lacosamide showed positive effects on reducing free radicals, improving mitochondrial enzymatic activity, and protecting against oxidative stress and DNA damage induced by repeated PTZ administration.
This study evaluated the effect of lacosamide (LCM) on biochemical and mitochondrial parameters after PTZ kindling in mice. Male mice were treated on alternative days for a period of 11 days with LCM (20, 30, or 40 mg/kg), saline, or diazepam (2 mg/kg), before PTZ administration (50 mg/kg). The hippocampi were collected to evaluate free radicals, the activities of superoxide dismutase (SOD), catalase (CAT), and the mitochondrial complexes I-III, II, and II-III, as well as Bcl-2 and cyclo-oxygenase-2 (COX-2) expressions. Hippocampi, blood, and bone marrow were collected for genotoxic and mutagenic evaluations. LCM 40 mg/kg increased latency and decreased percentage of seizures, only on the 3rd day of observation. The dose of 30 mg/kg only showed positive effects on the percentage of seizures on the 2nd day of observation. LCM decreased free radicals and SOD activity and the dose of 40 mg/kg were able to increase CAT activity. LCM 30 and 40 mg/kg improved the enzymatic mitochondrial activity of the complex I-III and LCM 30 mg/kg improved the activity of the complex II. In the comet assay, the damage induced by PTZ administration was reduced by LCM 20 and 30 mg/kg. The dose of 20 mg/kg increased COX-2 expression while the highest dose used, 40 mg/kg, was able to reduce this expression when compared to the group treated with LCM 20 mg/kg. Although LCM did not produce the antiepileptogenic effectin vivo, it showed the neuroprotective effect against oxidative stress, bioenergetic dysfunction, and DNA damage induced by the repeated PTZ administration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据