An in vitro study of new antiepileptic drugs and astrocytes

Purpose: The aim of our research was to study some biochemical modifications elicited in primary rat astrocyte cultures by treatment with gabapentin (GBP), carbamazepine (CBZ), lamotrigine (LTG), topiramate (TPM), oxcarbazepine (OXC), tiagabine (TGB), and levetiracetam (LEV), commonly used in the treatment of epilepsy. We investigated the biologic effects of these anticonvulsants (AEDs) at concentrations of 1, 10, 50, and 100 μg/ml. Methods: The study was performed by examining cell viability (MTT assay), cell toxicity [lactate dehydrogenase (LDH) release in the medium], glutamine synthetase (GS) activity, reactive oxygen species (ROS) production, lipoperoxidation level (malondialdehyde; MDA), and DNA fragmentation (COMET assay). The level of the expression of 70-kDa heat-shock protein (HSP70) and inducible nitric oxide synthase (iNOS) as oxidative stress-modulated genes also was determined. Results: Our experiments indicate that CBZ, TPM, and OXC induce stress on astrocytes at all concentrations. GBP, LTG, TGB, and LEV, at low concentrations, do not significantly change the metabolic activities examined and do not demonstrate toxic actions on astrocytes. They do so at higher concentrations. Conclusions: Most AEDs have effects on glial cells and, when used at an appropriate cell-specific concentrations, may be well tolerated by cortical astrocytes. However, at higher concentrations, GBP, LTG, TGB, and LEV seem to be better tolerated than are CBZ, TPM, and OXC. These findings may reveal novel ways of producing large numbers of new AEDs capable of reducing the extent of inflammation, neuronal damage, and death under pathological conditions such as epilepsy and/or traumatic brain injury.