title: Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, Medical Chemistry and Molecular Biology, Section of Biological Chemistry, University of Catania, Italy. livolti@unict.it
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Agata
authors.initials: A
authors.lastname: Campisi
authors.forename: Paolo
authors.initials: P
authors.lastname: Murabito
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Raciti
authors.forename: Roberto
authors.initials: R
authors.lastname: Avola
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mangiameli
authors.forename: Ilenia
authors.initials: I
authors.lastname: Musumeci
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Barcellona
authors.forename: Angelo
authors.initials: A
authors.lastname: Vanella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D020552:Comet Assay; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D051547:Heme Oxygenase-1; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D018686:Anesthetics, Intravenous; D013778:Tetrazolium Salts; D013844:Thiazoles; D030421:Peroxynitrous Acid; C002385:linsidomine; D004247:DNA; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D015742:Propofol