title: Dehydroascorbic acid normalizes several markers of oxidative stress and inflammation in acute hyperglycemic focal cerebral ischemia in the rat.
abstract: We investigated the effect of dehydroascorbic acid (DHA), the oxidized form of vitamin C which is a superoxide scavenger, on manganese superoxide dismutase (MnSOD), copper-zinc SOD (CuZnSOD), cyclooxygenase-2 (COX-2) and interleukin-1beta (IL-1beta) expression in a rat model of focal cerebral ischemia under normo- and hyperglycemic conditions. Edema formation was also assessed. MnSOD, CuZnSOD, COX-2 and IL-1beta mRNA and protein expression were studied 3 h post-ischemia. No changes were observed in MnSOD and CuZnSOD mRNA expression among the groups. COX-2 and IL-1beta mRNA expression were upregulated by ischemia but were not influenced by the glycemic state. At the protein level, hyperglycemic cerebral ischemia increased MnSOD and CuZnSOD [Bémeur, C., Ste-Marie, L., Desjardins, P., Butterworth, R.F., Vachon, L., Montgomery, J., Hazell, A.S., 2004a. Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat. Neurochem. Int. 45, 1167-1174] and IL-1beta expression compared to normoglycemic ischemia. COX-2 protein expression was also significantly higher following hyperglycemic ischemia compared to hyperglycemic shams. DHA administration did not change the pattern of COX-2 or IL-1beta mRNA expression, but normalized the increased protein expression following hyperglycemic ischemia. DHA administration also normalized MnSOD and CuZnSOD protein expression to the levels observed in normoglycemic ischemic animals. Edema formation was significantly reduced by DHA administration in hyperglycemic ischemic animals. The DHA-induced post-transcriptional normalization of MnSOD, CuZnSOD, COX-2 and IL-1beta levels and the decreased edema formation suggest that hyperglycemia accelerates superoxide formation and the inflammatory response, thus contributing to early damage in hyperglycemic stroke and strategies to scavenge superoxide should be an important therapeutic avenue.
authors.affiliation: Laboratoire de Neurobiologie, PEA A-423, Centre de Recherche du CHUM, Hôpital St-Luc, 1058 St-Denis, Montréal, Québec, Canada H2X 3J4. chan.chan@videotron.ca
authors.forename: Chantal
authors.initials: C
authors.lastname: Bémeur
authors.forename: Line
authors.initials: L
authors.lastname: Ste-Marie
authors.forename: Paul
authors.initials: P
authors.lastname: Desjardins
authors.forename: Luc
authors.initials: L
authors.lastname: Vachon
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
authors.forename: Alan S
authors.initials: AS
authors.lastname: Hazell
authors.forename: Jane
authors.initials: J
authors.lastname: Montgomery
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051546:Cyclooxygenase 2; D003683:Dehydroascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D007375:Interleukin-1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013481:Superoxides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; D003683:Dehydroascorbic Acid