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 M, 80 microM, 160 microM, and 1 mM). The protective effects of propofol were evaluated by 3(4,5-dimethyl-thiazol--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 kB 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.

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

ACQUAVIVA, ROSARIA;CAMPISI, Agatina;MURABITO P;RACITI, Giuseppina;AVOLA, Roberto;LI VOLTI, Giovanni
2004

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 M, 80 microM, 160 microM, and 1 mM). The protective effects of propofol were evaluated by 3(4,5-dimethyl-thiazol--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 kB 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.
Heme Oxygenase; peroxynitrite; primary cultured astrocytes; apoptosis; DNA damage; propofol
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/4193
Citazioni
  • ???jsp.display-item.citation.pmc??? 19
  • Scopus 89
  • ???jsp.display-item.citation.isi??? 81
social impact