Levetiracetam protects against kainic acid-induced toxicity.
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-1beta (IL-1beta) 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 micromol/g protein; KA + LVT = 15 +/- 2 micromol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 +/- 0.8 micromol/g protein; KA + LVT = 13 +/- 0.3 micromol/g protein; P < 0.05), reduced brain IL-1beta 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.
Marini
Herbert
H
Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Azienda Ospedaliera Universitario "G. Martino", Torre Biologica 5th Floor Via Consolare Valeria Gazzi, 98100 Messina, Italy.
Costa
Cinzia
C
Passaniti
Maria
M
Esposito
Maria
M
Campo
Giuseppe M
GM
Ientile
Riccardo
R
Adamo
Elena Bianca
EB
Marini
Rolando
R
Calabresi
Paolo
P
Altavilla
Domenica
D
Minutoli
Letteria
L
Pisani
Francesco
F
Squadrito
Francesco
F
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000077287:Levetiracetam; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control*; D018697:Nootropic Agents / Q000494:pharmacology*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018690:Excitatory Amino Acid Agonists; D007375:Interleukin-1; D018697:Nootropic Agents; D000077287:Levetiracetam; D008315:Malondialdehyde; D012313:RNA; D005978:Glutathione; D007608:Kainic Acid; D010889:Piracetam