Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme

Brain Res. 2010 Jul 9;1343:178-85. doi: 10.1016/j.brainres.2010.04.036. Epub 2010 Apr 24.

Abstract

Neonatal hypoxia-ischemia (HI) brain injury involves reactive oxygen species (ROS) and inflammatory responses. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has cytoprotective effects against oxidative stress and its effect was mediated by NF-E2-related factor-2 (Nrf2), a transcription factor, and heme oxygenase 1 (HO-1) which is one of Nrf2 downstream target genes. This study was undertaken to investigate the neuroprotective mechanisms of SFN in a neonatal HI rat model. Seven-day-old rat pups were subjected to left common carotid artery ligation and hypoxia (8% oxygen at 37 degrees C) for 90 min. SFN (5mg/kg) was systemically administered 30 min before HI insult. Brain injury was assessed by 2,3,5-triphenyltetrazoliumchloride (TTC), Nissl, TUNEL staining, malondialdehyde (MDA), 8OH-dG level, and caspase-3 activity in the cortex and hippocampus. SFN pretreatment increased the expression of Nrf2 and HO-1 in the brain and reduced infarct ratio at 24h after HI. The number of TUNEL-positive neurons as well as activated macroglia and the amount of 8OH-dG, were markedly reduced after SFN treatment, accompanied by suppressed caspase-3 activity and reduced lipid peroxidation (MDA) level. These results demonstrated that SFN could exert neuroprotective effects through increasing Nrf2 and HO-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Enzyme Induction / drug effects
  • Enzyme Induction / physiology
  • Heme Oxygenase (Decyclizing) / physiology
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / enzymology*
  • Hypoxia-Ischemia, Brain / pathology
  • Isothiocyanates
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis*
  • NF-E2-Related Factor 2 / physiology*
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / pathology
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Second Messenger Systems / drug effects
  • Second Messenger Systems / physiology
  • Thiocyanates / pharmacology*
  • Thiocyanates / therapeutic use

Substances

  • Biomarkers
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Thiocyanates
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • NAD(P)H Dehydrogenase (Quinone)
  • sulforafan