Effect of lamotrigine, levetiracetam & topiramate on neurobehavioural parameters & oxidative stress in comparison with valproate in rats

Abstract

Background & objectives:Though newer antiepileptic drugs are considered safer than conventional antiepileptics, the effects of lamotrigine, levetiracetam and topiramate on neurobehavioural functions are yet to be established. This study evaluated neurobehavioural parameters and oxidative stress markers in brain tissue of rats treated with lamotrigine, levetiracetam and topiramate compared to sodium valproate.Methods:Five groups of male Wistar rats were treated respectively with normal saline (control), sodium valproate (370 mg/kg), lamotrigine (50 mg/kg), levetiracetam (310 mg/kg) and topiramate (100 mg/kg) for 45 days. Neurobehavioural parameters were assessed using elevated plus maze (EPM), actophotometer, rotarod, passive avoidance and Morris water maze (MWM) at baseline and at the end of treatment. Oxidative stress parameters [malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD)] were estimated in rat brain at the end of treatment.Results:Valproate and lamotrigine showed no significant effect on learning and memory in passive avoidance and MWM tests. However, levetiracetam and topiramate reduced retention memory significantly as compared to control (P<0.01) and lamotrigine (P<0.05) groups. Performances on EPM, rotarod and actophotometer were not significantly different between the groups. In comparison to control group, MDA was higher in the levetiracetam and topiramate (360.9 and 345.9 nmol/g of homogenized brain tissue, respectively) groups. GSH and SOD activity were significantly reduced by valproate and levetiracetam treatment. Lamotrigine did not induce significant oxidative stress.Interpretation & conclusions:Long-term and therapeutic dose treatment with levetiracetam and topiramate significantly impaired learning and memory, which was not seen with valproate and lamotrigine in rats. Levetiracetam, topiramate and valproate augmented oxidative stress, whereas lamotrigine has little effect on it. These antiepileptic drugs are used in clinical practice, hence pharmacovigilance studies are required to evaluate their safety profile.

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

“…Literature data have shown that AEDs such as TPM and levetiracetam can induce lipid peroxidation and impair the antioxidant defense system in naive rats, while the same drugs produce a disease-modifying effect with antioxidant potency both in patients and experimental models of acquired epilepsy [ 38 , 39 , 40 ]. Moreover, new AEDs such as lamotrigine and oxcarbazepine may have pronounced beneficial effects in epileptic and nonepileptic conditions while the first-generation medications such as phenytoin, phenobarbital, and carbamazepine may trigger additional oxygen-dependent tissue injury in epileptic patients [ 41 , 42 ].…”

Ferroptosis and Its Role in Epilepsy

“…In epileptic patients receiving phenytoin monotherapy, the level of serum malondialdehyde was significantly increased, whereas the GSH level was significantly decreased. However, no significant changes in these parameters were observed in epileptic patients treated with carbamazepine or lamotrigine monotherapy, which were found to result in less disturbance to lipid peroxidation (Liu et al, 1998;Sarangi et al, 2016). Selenium and topiramate combination supplementation increases erythrocyte GSH and GPX4 and plasma concentrations of vitamins A and C in epileptic patients (Yürekli and Nazıroglu, 2013).…”