Enoxaparin pretreatment alleviates pentylenetetrazol–induced epileptic seizures in Wistar rats

Epilepsy, is a prevalent neurological disorder characterized by recurring seizures. A low molecular weight heparin enoxaparin has multifaceted properties. In addition to its anticoagulant activity, enoxaparin has demonstrated anti–inflammatory, antioxidant and anti–apoptotic effects. Accordingly, the purpose of this study was to evaluate the protective effect of enoxaparin against seizures, oxidative stress, proinflammatory cytokines, apoptosis, brain–derived neurotropic factor (BDNF) concentrations and cognitive impairment in pentylenetetrazole (PTZ) induced kindling in Wistar rats. Twenty–four rats divided into 4 groups (Control, PTZ, ENX250+PTZ, ENX500+PTZ) were used. Enoxaparin (250 and 500 IU·kg-1, intraperitoneal –ip–) or vehicle (saline) were given to rats for 5 days. On the fifth day, 30 min after drug administration, PTZ (45 mg·kg-1, ip) was given to cause seizures. Behavioral seizure parameters were evaluated by video recording. A behavioral test, passive avoidance test was performed. PTZ administration decreased total antioxidant status (TAS) while increased total oxidant status (TOS) both in hippocampus and cortex. Furthermore, PTZ induced elevated levels of tumor necrosis factor alpha (TNF–α), interleukin–1β (IL–1β), BDNF, caspase–3, and caspase–9. Pretreatment with enoxaparin decreased the levels of these parameters and TOS, while increased TAS. Enoxaparin pretreatment significantly decreased the epileptic seizure scores according to the Racine scale, increased first myoclonic jerk (FMJ) time and the test trial time in passive avoidance test. These results indicate that enoxaparin (250 and 500 IU·kg-1) at both doses has promising protective effect against PTZ induced epilepsy by improving memory impairment, inflammation, oxidative stress and apoptosis. This positive effect was more prominent at 500 IU·kg-1 dose of enoxaparin.