Analysis of oxidative stress in SK-N-MC neurons exposed to styrene-7,8-oxide.
Styrene-7,8-oxide (SO) is the main metabolite of styrene, a neurotoxic volatile organic compound used industrially. Here we report the novel observation that several markers of oxidative stress were affected in SK-N-MC cells exposed for 16 h to concentrations of SO that induce apoptotic cell death. The production of Thiobarbituric Acid Reactive Substances (TBARS), rose from 69.1 +/- 15.7 nmol/g protein (control) to 119.3 +/- 39.2 and 102.0 +/- 17.3 nmol/g protein after exposure to 0.3 and 1 mM SO, respectively. Carbonyl group levels were significantly enhanced by SO at both concentrations. The lower dose also decreased sulphydryl groups. SO caused a marked oxidative DNA damage, as shown by a fivefold increase in 8-hydroxy-2(')-deoxyguanosine (8-OHdG). In addition, SO exposure resulted in alterations of scavenging abilities, given the reduction of both glutathione (GSH) and glutathione-S-transferase (GST) activity. Induction of expression of the oxidative stress response gene heme-oxygenase-1 (HO-1) and an increased HO-1 activity were also observed. These data provide compelling evidence that oxidative stress significantly contributes to SO toxicity in neuronal cells.
Vettori
M V
MV
ISPESL Research Center at the University of Parma, via Gramsci 14, Parma 43100, Italy. mariavittoria.vettori@unipr.it
Caglieri
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A
Goldoni
M
M
Castoldi
A F
AF
Darè
E
E
Alinovi
R
R
Ceccatelli
S
S
Mutti
A
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015415:Biomarkers; D002273:Carcinogens; D004852:Epoxy Compounds; D016166:Free Radical Scavengers; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D000080242:8-Hydroxy-2'-Deoxyguanosine; C013690:styrene oxide; D005982:Glutathione Transferase; D003849:Deoxyguanosine; D005978:Glutathione