To Investigate the Synergistic Potential of Limonene and Vinpocetine in Pentylenetetrazole-Induced Kindling in Rats

Abstract

Epilepsy is a chronic neurological disease characterized by an enduring propensity for generation of seizures. The burden of comorbidity including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and arthritis are up to eight times more common in people with epilepsy than in the general population. Increased oxidative stress and inflammation with decreased activity of glutathione peroxidase, superoxide dismutase (SOD), and catalase has been observed in patients with epilepsy. The present study was designed to investigate the synergistic potential of limonene and vinpocetine in Pentylenetetrazole-induced kindling in rats. Pharmacoresistant epilepsy in humans is resembled to kindling in animal models. For PTZ kindling, a sub convulsant dose of PTZ (30 mg/kg) was injected intraperitoneally on every alternate day for 23 days. Limonene (25 mg/kg), vinpocetine (10 mg/kg) and the combination of vinpocetine (10mg/kg) along with limonene (25mg/kg) were administered from 7th to 34th day. Open field test and elevated plus maze were used to assess locomotor impairment and anxious behaviour of experimental animals. Morris water maze was employed to assess spatial learning and memory. Biochemical parameters like reduced glutathione (GSH), catalase, Malondialdehyde (MDA) and nitrite levels in cortical and hippocampal regions were used to mark the oxidative-nitrosative stress caused due to PTZ administration. Limonene and vinpocetine treatment had attenuated the PTZ induced behavioural and biochemical abnormalities in rats. Also, limonene and vinpocetine treatment results in amelioration of neuronal damage induced due to PTZ administration assessed in histopathological examination. Based on current observations it could be concluded that the combination of vinpocetine and limonene may reverse the comorbidities associated with PTZ kindling in rat though their antioxidant activity and neuroprotective potential. However further studies are required to explore synergy.