Modulation of IL-1 β gene expression by lipid peroxidation inhibition after kainic acid-induced rat brain injury

Herbert Marini, Domenica Altavilla, Maria Bellomo, Elena Bianca Adamo, Rolando Marini, Floriana Laureanti, Maria Carmela Bonaccorso, Paolo Seminara, Maria Passaniti, Letteria Minutoli, Alessandra Bitto, Gioacchino Calapai, Francesco Squadrito

Research output: Contribution to journalArticlepeer-review

Abstract

Brain injury was induced by intraperitoneal administration of kainic acid (KA, 10 mg/kg). Animals were randomized to receive either IRFI 042 (20 mg/kg i.p.), a lipid peroxidation inhibitor, or its vehicle (NaCl 0.9% DMSO 10% 1 ml/kg i.p.) 30 min before KA administration. A first set of animals was sacrificed 6 h after KA injection to measure malondialdehyde (MDA) content, glutathione-reduced (GSH) levels and the mRNA for interleukin-1β (IL-1β) in the cortex and in the hippocampus. A second set of animals was sacrificed 48 h after KA administration for histological analysis. All animals were observed for monitoring the behavioral sequelae and for evaluating latency of convulsions. Sham brain injury rats were used as controls. Intraperitoneal administration of IRFI 042 significantly decreased brain MDA (cortex: KA + vehicle = 0.285 ± 0.04 nmol/mg protein; KA + IRFI 042 = 0.156 ± 0.02 nmol/mg protein, P <0.005; hippocampus: KA + vehicle = 0.350 ± 0.03 nmol/mg protein; KA + IRFI 042 = 0.17 ± 0.04 nmol/mg protein, P <0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 7.81 ± 1 μmol/g protein; KA + IRFI 042 = 12.1 ± 1 μmol/g protein; P <0.005) and hippocampus (KA + vehicle = 5 ± 0.8 μmol/g protein; KA + IRFI 042 = 9.4 ± 1.8 μmol/g protein; P <0.005), reduced both brain IL-1β mRNA expression and oedema, and increased latency of convulsions. Histological analysis showed a reduction of cell damage in IRFI 042-treated samples. The present data indicate that lipid peroxidation inhibition reduces IL-1β gene expression and protects against kainic acid-induced brain damage.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalExperimental Neurology
Volume188
Issue number1
DOIs
Publication statusPublished - Jul 2004

Keywords

  • Brain damage
  • Gene expression
  • IL-1 β
  • Kainic acid

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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