Diphenyl diselenide and 2,3-dimercaptopropanol increase the PTZ-induced chemical seizure and mortality in mice

Brain Res Bull. 2006 Feb 15;68(6):414-8. doi: 10.1016/j.brainresbull.2005.09.007. Epub 2005 Oct 3.

Abstract

The aim of the present study was to evaluate the interaction between a classic GABAergic antagonist -- pentylenetetrazol (PTZ) with an organoselenium compound -- diphenyl diselenide (PhSe)(2) and with the metal chelating agent -- 2,3 dimercaptopropanol (BAL). Mice were pre-treated with 150 micromol/kg (PhSe)(2) or BAL (250, 500 or 1000 micromol/kg) before treatment with PTZ. Pre-treatment with (PhSe)(2) reduced the latency for PTZ-induced seizure at doses of 40 and 60 mg/kg and cause a decrease in the latency for PTZ-induced death at the dose of 60 mg/kg. However, treatment with PTZ at dose of 80 mg/kg was not affected by (PhSe)(2) pre-treatment. Pre-treatment with BAL reduced the latency for PTZ-induced seizure at doses of 40 and 50 mg/kg. In addition, the latency for PTZ-induced death at the dose of 40 mg/kg was decreased significantly by pre-treatment with all doses of BAL. At the dose of 50mg/kg, a significant decrease in the latency for death occurred only in mice pre-treated with 500 and 1000 micromol/kg of BAL. Our results indicate that the PTZ-induced chemical seizures and mortality was enhanced by (PhSe)(2) and BAL. These results indicated that (PhSe)(2) and BAL interact with PTZ possibly by modulating the GABAergic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzene Derivatives / toxicity*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Chelating Agents / toxicity
  • Convulsants / toxicity*
  • Dimercaprol / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • GABA Antagonists / toxicity
  • Male
  • Mice
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Organoselenium Compounds / toxicity*
  • Pentylenetetrazole / toxicity*
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, GABA / drug effects
  • Receptors, GABA / metabolism
  • Seizures / chemically induced*
  • Seizures / metabolism
  • Seizures / physiopathology
  • Survival Rate
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Benzene Derivatives
  • Chelating Agents
  • Convulsants
  • GABA Antagonists
  • Organoselenium Compounds
  • Receptors, GABA
  • Dimercaprol
  • diphenyldiselenide
  • gamma-Aminobutyric Acid
  • Pentylenetetrazole