N-acetylcysteine Selectively Protects Cerebellar Granule Cells From 4-hydroxynonenal-induced Cell Death

Neurosci Res. 2006 Jul;55(3):255-63. doi: 10.1016/j.neures.2006.03.008. Epub 2006 May 3.

Abstract

4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, has been shown to induce neurotoxicity accompanied by multiple events. To clarify mechanisms of neuroprotective compounds on HNE-induced toxicity, the protective effects of N-acetylcysteine (NAC), alpha-tocopherol (TOC), ebselen and S-allyl-L-cysteine (SAC) were compared in cerebellar granule neurons. The decrease in MTT reduction induced by HNE was significantly suppressed by pretreatment of the neurons with 1000 microM NAC or 10 and 100 microM TOC; however, lactate dehydrogenase (LDH) release and propidium iodide (PI) fluorescence studies revealed that neuronal death was suppressed by NAC but not by TOC. Treatment of these neurons with HNE resulted in a drastic reduction of mitochondrial membrane potential, and this reduction was also prevented by NAC but not by TOC. Ebselen and SAC, a garlic compound, were unable to protect these neurons against HNE-induced toxicity. Pretreatment with NAC also prevented HNE-induced depletion of intracellular glutathione (GSH) levels in these neurons. These results suggest that NAC, but not other antioxidants such as TOC, SAC and ebselen, exerts significant protective effects against HNE-induced neuronal death in cerebellar granule neurons, and that this neuroprotective effect is due, at least in part, to preservation of mitochondrial membrane potential and intracellular GSH levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Acetylcysteine / therapeutic use
  • Aldehydes / antagonists & inhibitors*
  • Aldehydes / toxicity
  • Animals
  • Animals, Newborn
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use
  • Glutathione / drug effects
  • Glutathione / metabolism
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / prevention & control
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Neurotoxins / antagonists & inhibitors
  • Neurotoxins / toxicity
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Wistar

Substances

  • Aldehydes
  • Antioxidants
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Neurotoxins
  • Plant Extracts
  • L-Lactate Dehydrogenase
  • Glutathione
  • 4-hydroxy-2-nonenal
  • Acetylcysteine