Dehydroascorbic acid normalizes several markers of oxidative stress and inflammation in acute hyperglycemic focal cerebral ischemia in the rat

Neurochem Int. 2005 Apr;46(5):399-407. doi: 10.1016/j.neuint.2004.11.007.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Brain Edema / drug therapy
  • Brain Edema / physiopathology
  • Brain Edema / prevention & control
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / physiopathology
  • Cyclooxygenase 2
  • Dehydroascorbic Acid / pharmacology*
  • Dehydroascorbic Acid / therapeutic use
  • Disease Models, Animal
  • Encephalitis / drug therapy*
  • Encephalitis / metabolism
  • Encephalitis / physiopathology
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use
  • Hyperglycemia / complications
  • Hyperglycemia / metabolism
  • Hyperglycemia / physiopathology
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxides / antagonists & inhibitors
  • Superoxides / metabolism


  • Biomarkers
  • Free Radical Scavengers
  • Interleukin-1
  • Neuroprotective Agents
  • RNA, Messenger
  • Superoxides
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Superoxide Dismutase
  • Dehydroascorbic Acid