Role of the trace metals, selenium and zinc, in pilocarpine-induced epilepsy in rats

ABSTRACT

Excitotoxic brain lesions, such as epilepsy, lead to increasing destruction of neurons, in the course of few hours after the insult. The deadly cascade of events possibly involves detrimental actions by free radicals, proinflammatory cytokines and the activation of pro-apoptotic transcription factors, which finally result in neuronal destruction. Several reports suggest that the level of some trace elements play a vital role in seizure conditions to prevail. The aim of the present study was to assess the possible modulatory role of the trace elements, selenium and zinc on pilocarpine-induced epilepsy in rats.The study was carried out on 40 male albino rats, weighing 150-200 grams that were divided into the following groups each of 10 rats Group I control rats that received intraperitoneal [i.p.] saline, Group II pilocarpine induced epilepsy, Group 111 selenium pretreated for 3 weeks before pilocarpine injection and Group IV zinc pretreated for 3 weeks before pilocarpine injection. The seizure latency and severity for each rat was recorded. Twenty four hours following pilocarpine injection, rats were exsanguinated and the following parameters were determined cerebral caspase-3 activity [as a marker of apoptosis], interleukin-lbeta [IL-ljB], reduced glutathione [GSH] and malondialdehyde [MDA] concentrations, serum neuron specific enolase[NSE] concentration [as a marker of brain injury].Intraperitoneal injection of pilocarpine in rats resulted in progression to limbic seizures with progressing behavioural scores at various time intervals [recorded every 30 minutes up to 2 hours]. Latency to forelimb clonus was 51.86 +/- 1.89 min. The results of the present study demonstrated significantly increased cerebral MDA concentration together with significant decrease in cerebral GSH concentration in non-treated pilocarpine injected rats compared to normal control rats. A significant increase in cerebral caspase-3 activity, and in cerebral 1L-1/beta as well as in serum NSE concentrations could be observed in non-treated pilocarpine-injected rats compared to normal control rats. Pretreatment with selenium or zinc reduced the severity of pilocarpine- induced seizures. In addition, both trace elements decreased the latency to attain the forelimb clonus [score 4]. A significant decrease in cerebral MDA and IL-1/beta, serum NSE concentrations could be observed in selenium and zinc-treated rats compared to non-treated pilocarpine-injected rats. A significant' increase in cerebral GSH concentration was observed in zinc-treated, but not in selenium-treated ones.The results of the present study confirm the role of the trace elements, selenium and zinc, in mitigating epilepsy. Further human studies to evaluate the role of trace elements in epilepsy are recommended. Furthermore, since antiepileptic drugs [AEDs] are reported to induce zinc and selenium deficiency,thus combining these trace elements with AEDs are worthy to be evaluated