Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ-kindling model in mice.

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 11days with LCM (20, 30, or 40mg/kg), saline, or diazepam (2mg/kg), before PTZ administration (50mg/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 40mg/kg increased latency and decreased percentage of seizures, only on the 3rd day of observation. The dose of 30mg/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 40mg/kg were able to increase CAT activity. LCM 30 and 40mg/kg improved the enzymatic mitochondrial activity of the complex I-III and LCM 30mg/kg improved the activity of the complex II. In the comet assay, the damage induced by PTZ administration was reduced by LCM 20 and 30mg/kg. The dose of 20mg/kg increased COX-2 expression while the highest dose used, 40mg/kg, was able to reduce this expression when compared to the group treated with LCM 20mg/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.