Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus.
Statins may act on inflammatory responses, decreasing oxidative stress and also reducing temperature after a brain ischemic insult. Previous data have indicated that statins protect neurons from death during long-lasting status epilepticus (SE) and attenuate seizure behaviors in animals treated with kainic acid. In this context, the study described here aimed to investigate the effect of lovastatin on body temperature and on mRNA expression levels of hippocampal cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 and B2 receptors of rats submitted to pilocarpine-induced SE. Quantitative real-time polymerase chain reaction showed a significant decrease in mRNA expression of interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 receptor in animals with SE treated with lovastatin, compared with untreated animals with SE (P<0.001). Lovastatin also reduced SE-induced hyperthermia, indicating that mechanisms related to brain protection are triggered by this drug under conditions associated with acute excitotoxicity or long-lasting SE.
Departamento de Neurologia e Neurocirurgia da Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil.
Telma Luciana Furtado
TL
Gouveia
Fulvio Alexandre
FA
Scorza
Michele Juliana Vieira
MJ
Silva
Tatiane de Aquino
Tde A
Bandeira
Sandra Regina
SR
Perosa
Gustavo Adolfo
GA
Argañaraz
Marcelo de Paula
Mde P
Silva
Thiago Rodrigues
TR
Araujo
Maria Isabel Berzaghi
MI
Frangiotti
Débora
D
Amado
Esper Abrão
EA
Cavalheiro
José Antonio
JA
Silva
Maria da Graça
Mda G
Naffah-Mazzacoratti
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005334:Fever / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010862:Pilocarpine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D012333:RNA, Messenger; D010862:Pilocarpine; D008148:Lovastatin