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Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ-kindling model in mice.
- Source :
-
Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2021 Apr; Vol. 35 (2), pp. 351-363. Date of Electronic Publication: 2020 Aug 26. - Publication Year :
- 2021
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Abstract
- 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 effect in vivo, it showed the neuroprotective effect against oxidative stress, bioenergetic dysfunction, and DNA damage induced by the repeated PTZ administration.<br /> (© 2020 Société Française de Pharmacologie et de Thérapeutique.)
Details
- Language :
- English
- ISSN :
- 1472-8206
- Volume :
- 35
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Fundamental & clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32851690
- Full Text :
- https://doi.org/10.1111/fcp.12598