Levetiracetam protects against kainic acid-induced toxicity

Herbert Marini, Cinzia Costa, Maria Passaniti, Maria Esposito, Giuseppe M. Campo, Riccardo Ientile, Elena Bianca Adamo, Rolando Marini, Paolo Calabresi, Domenica Altavilla, Letteria Minutoli, Francesco Pisani, Francesco Squadrito

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1β (IL-1β) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 ± 0.03 nmol/mg protein; KA + LVT = 0.13 ± 0.01 nmol/mg protein; P <0.005), and in the diencephalons (KA + vehicle = 1,01 ± 0.2 nmol/mg protein; KA + LVT = 0,33 ± 0,08 nmol/mg protein; P <0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 ± 1 μmol/g protein; KA + LVT = 15 ± 2 μmol/g protein; P <0.005) and diencephalons (KA + vehicle = 9 ± 0.8 μmol/g protein; KA + LVT = 13 ± 0.3 μmol/g protein; P <0.05), reduced brain IL-1β mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuro-protective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation.

Original languageEnglish
Pages (from-to)1253-1264
Number of pages12
JournalLife Sciences
Volume74
Issue number10
DOIs
Publication statusPublished - Jan 23 2004

Keywords

  • Kainic acid
  • Levetiracetam
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology

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