Protective effect of 2,2'-dithienyl diselenide on kainic acid-induced neurotoxicity in rat hippocampus

Neuroscience. 2011 Oct 13:193:300-9. doi: 10.1016/j.neuroscience.2011.07.038. Epub 2011 Jul 27.

Abstract

In this study, we investigated the effects of 2,2'-dithienyl diselenide (DTDS), an organoselenium compound, against seizures induced by kainic acid (KA) in rats. Rats were pretreated with DTDS (50 or 100 mg/kg) by oral route 1 h before KA injection (10 mg/kg, intraperitoneal). Our results showed that DTDS (100 mg/kg) was effective in increasing latency for the onset of the first clonic seizure episode induced by KA, as well as in decreasing the appearance of seizures and the Racine's score. DTDS also caused a decrease in the excitatory electroencephalographic (EEG) changes, resulting from KA exposure in hippocampus and cerebral cortex of rats. Besides, elevated reactive species (RS) and carbonyl protein levels and Na(+), K(+)-ATPase activity in hippocampus of rats treated with KA were ameliorated by DTDS (50 and 100 mg/kg). Lastly, as evidenced by Cresyl-Violet stain, DTDS (100 mg/kg) elicited a protective effect against KA-induced neurodegeneration in rat hippocampus 7 days after KA injection. In conclusion, the present study showed that DTDS attenuated KA-induced status epilepticus in rats and the subsequent hippocampal damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electroencephalography
  • Glutathione Peroxidase / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Kainic Acid / toxicity
  • Male
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / therapeutic use*
  • Neurotoxicity Syndromes / complications
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology*
  • Neurotoxicity Syndromes / prevention & control*
  • Neurotoxins / toxicity
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / therapeutic use*
  • Oxidative Stress / drug effects
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Seizures / etiology
  • Seizures / prevention & control
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Sulfhydryl Compounds / metabolism
  • Thiophenes / chemistry
  • Thiophenes / therapeutic use*
  • Thymidine / analogs & derivatives*
  • Thymidine / chemistry
  • Thymidine / therapeutic use
  • Trityl Compounds / chemistry
  • Trityl Compounds / therapeutic use*

Substances

  • 2,2'-dithienyl diselenide
  • Neuroprotective Agents
  • Neurotoxins
  • Organoselenium Compounds
  • Sulfhydryl Compounds
  • Thiophenes
  • Triphenylmethyl Compounds
  • 5'-O-(4,4'-dimethoxytrityl)thymidine-3'-O-(2,4-dinitrophenyl) succinate
  • Glutathione Peroxidase
  • Sodium-Potassium-Exchanging ATPase
  • Kainic Acid
  • Thymidine