title: 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)E(2), 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 with 10 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 PGE(2) 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Str, 11562 Cairo, Egypt.
authors.forename: Muhammad Y
authors.initials: MY
authors.lastname: Al-Shorbagy
authors.forename: Bahia M
authors.initials: BM
authors.lastname: El Sayeh
authors.forename: Dalaal M
authors.initials: DM
authors.lastname: Abdallah
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018021:Lithium Chloride; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy; D018375:Neutrophil Activation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D010862:Pilocarpine; D016753:Interleukin-10; D009569:Nitric Oxide; D003907:Dexamethasone; D018021:Lithium Chloride; D015232:Dinoprostone