Diverse effects of variant doses of dexamethasone in lithium–pilocarpine induced seizures in rats

Abstract

Corticosteroids are used in the management of several epileptic aliments; however, their effectiveness in combating seizures remains controversial, with pro- and anti-convulsive effects ascribed. The current study aimed to address the modulatory effect of dexamethasone (DEX) utilizing 3 dose levels (5, 10, and 20 mg/kg body mass of male Wistar rat) in the rat lithium–pilocarpine (Li-PIL) epilepsy model. Li-PIL induced seizures that were associated with neuronal cell loss in the CA3 region, and increased prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide, and neutrophil infiltration in the hippocampus. However, Li-PIL compromised the oxidant–antioxidant balance of the hippocampus. Effective anticonvulsant activity was only observed with10 mg DEX/kg body mass, which reduced seizure production and incidence, as well as neuronal cell loss in the CA3 region. At this anticonvulsant dose, enhancements in the antioxidant system and IL-10, as well as suppression of altered inflammatory markers were observed. Conversely, doubling the dose showed a tendency to shorten seizure latency, and neither affected seizure incidence nor CA3 neuronal cell loss. These effects were associated with an increase in levels of PGE2 and TNF-α. The present study found a lack of protection at 5 mg DEX/kg body mass, an anticonvulsant effect at 10 mg/kg, and a loss of protection at 20 mg/kg in the Li-PIL epilepsy model, which indicates that there is an optimal dose of DEX for preventing the induction of seizures.