Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism

Anesthesiology. 2004 Dec;101(6):1363-71. doi: 10.1097/00000542-200412000-00017.


Background: The concentration of peroxynitrite in the brain increases after central nervous system injuries. The authors hypothesized that propofol, because of its particular chemical structure, mitigates the effects of peroxynitrite-mediated oxidative stress and apoptosis by the induction of heme oxygenase (HO)-1 in primary cultured astroglial cells.

Methods: Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (3 mm SIN-1) in the presence or absence of propofol (40 microm, 80 microm, 160 microm, and 1 mm). The protective effects of propofol were evaluated by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide cytotoxicity assay, lactic dehydrogenase release, DNA ladderization by Comet assay, and caspase-3 activation by Western blot analysis.

Results: Appropriate propofol concentrations (ranging from 40 microm to 1 mm) significantly increased HO-1 expression and attenuated SIN-1-mediated DNA ladderization and caspase-3 activation. The protective effects of propofol were mitigated by the addition of tin mesoporphyrin, a potent inhibitor of HO activity. The addition of a specific synthetic inhibitor of nuclear factor kappaB abolished propofol-mediated HO-1 induction, suggesting a possible role of this nuclear transcriptional factor in our experimental conditions.

Conclusions: The antioxidant properties of propofol can be partially attributed to its scavenging effect on peroxynitrite as well as to its ability to increase HO-1 expression at higher concentrations, a property that might be relevant to neuroprotection during anesthesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Astrocytes / drug effects*
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • Comet Assay
  • DNA / chemistry
  • DNA / metabolism
  • DNA Damage / drug effects*
  • Enzyme Activation / drug effects
  • Heme Oxygenase (Decyclizing) / antagonists & inhibitors
  • Heme Oxygenase-1
  • L-Lactate Dehydrogenase / metabolism
  • Molsidomine / analogs & derivatives*
  • Molsidomine / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Peroxynitrous Acid / antagonists & inhibitors*
  • Propofol / pharmacology*
  • Rats
  • Rats, Wistar
  • Tetrazolium Salts
  • Thiazoles


  • Anesthetics, Intravenous
  • Tetrazolium Salts
  • Thiazoles
  • Peroxynitrous Acid
  • linsidomine
  • DNA
  • Molsidomine
  • L-Lactate Dehydrogenase
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • heme oxygenase-2
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • thiazolyl blue
  • Propofol