Dantrolene exerts protective activity in double and triple combination with nimodipine, ruthenium red and basilene blue in bilirubin-induced neurotoxicity in cell culture of rats

Int J Neurosci. 2009;119(10):1602-14. doi: 10.1080/00207450902794468.

Abstract

In the present study, dantrolene, nimodipine, basilen blue, and ruthenium red were tested in experimental bilirubin toxicity in cortical cell culture of rats. Neurotoxicity was induced by 10(-4) M bilirubin. Basilen blue in the highest concentration of 10(-4) M was determined as the most protective agent when applied alone. Dantrolene alone was found surprisingly ineffective in all doses tested. But it was found very protective both in double and triple combinations. Nimodipine, basilen blue, and ruthenim red neuroprotective potentials were enhanced by adding dantrolene into the media. Best double combination was determined as dantrolene plus ruthenium red. On the other hand, most useful triple combination was found as dantrolene plus nimodipine plus basilen blue. As a result, dantrolene wasn't found to be effective alone, while it seems most potential compound in combined application in bilirubin-induced neurotoxicity. The importance of calcium intrusion was confirmed in bilirubin-induced neurotoxicity.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antioxidants / toxicity
  • Bilirubin / toxicity
  • Calcium Channel Blockers / pharmacology*
  • Cell Death / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Dantrolene / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Interactions
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Nimodipine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Ruthenium Red / pharmacology*

Substances

  • Antioxidants
  • Calcium Channel Blockers
  • Drug Combinations
  • Neuroprotective Agents
  • Ruthenium Red
  • Nimodipine
  • Dantrolene
  • Bilirubin