title: Lovastatin decreases the synthesis of inflammatory mediators during epileptogenesis in the hippocampus of rats submitted to pilocarpine-induced epilepsy.
abstract: Statins may act on inflammatory responses, decreasing oxidative stress and also reducing brain inflammation in several brain disorders. Epileptogenesis is a process in which a healthy brain becomes abnormal and predisposed to generating spontaneous seizures. We previously reported that lovastatin could prevent neuroinflammation in pilocarpine-induced status epilepticus (SE). In this context, this study investigated the long-lasting effects of lovastatin on mRNA expression of proinflammatory cytokines (interleukin-1β, tumor necrosis factor α, interleukin-6) and the antiinflammatory cytokine IL-10 in the hippocampus during epileptogenesis by immunohistochemistry and real time polymerase chain reaction (RT-PCR) during the latent and chronic phases in the epilepsy model induced by pilocarpine in rats. For these purposes, four groups of rats were employed: saline (CONTROL), lovastatin (LOVA), pilocarpine (PILO), and pilocarpine plus lovastatin (PILO+LOVA). After pilocarpine injection (350mg/kg, i.p.), the rats were treated with 20mg/kg of lovastatin via an esophagic probe 2h after SE onset. All surviving rats were continuously treated during 15days, twice/day. The pilocarpine plus lovastatin group showed a significant decrease in the levels of IL-1β, TNF-α, and IL-6 during the latent phase and a decreased expression of IL-1β and TNF-α in the chronic phase when compared with the PILO group. Moreover, lovastatin treatment also induced an increased expression of the antiinflammatory cytokine, IL-10, in the PILO+LOVA group when compared with the PILO group in the chronic phase. Thus, our data suggest that lovastin may reduce excitotoxicity during epileptogenesis induced by pilocarpine by increasing the synthesis of IL-10 and decreasing proinflammatory cytokines in the hippocampus.
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: T L F
authors.initials: TL
authors.lastname: Gouveia
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Scorza
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: H A
authors.initials: HA
authors.lastname: Iha
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: M I B
authors.initials: MI
authors.lastname: Frangiotti
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: S R
authors.initials: SR
authors.lastname: Perosa
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: E A
authors.initials: EA
authors.lastname: Cavalheiro
authors.affiliation: Rehabilitation Department, Universidade Nove de Julho, São Paulo, Brazil.
authors.forename: J A
authors.initials: JA
authors.lastname: Silva
authors.affiliation: Rehabilitation Department, Universidade Nove de Julho, São Paulo, Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: Feliciano
authors.affiliation: Biomedical Engineering Department, Universidade Federal de São João del-Rei, São João del-Rei, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: de Almeida
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Biochemistry Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: naffahmazz.nexp@epm.br.
authors.forename: M G
authors.initials: MG
authors.lastname: Naffah-Mazzacoratti
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000924:Anticholesteremic Agents; D016207:Cytokines; D018721:Muscarinic Agonists; D012333:RNA, Messenger; D010862:Pilocarpine; D008148:Lovastatin
keywords: Cytokines; Epileptogenesis; Lovastatin; Pilocarpine; Temporal lobe epilepsy