Production of hydroxyl free radical by brain tissues in hyperglycemic rats subjected to transient forebrain ischemia

Free Radic Biol Med. 1999 Nov;27(9-10):1033-40. doi: 10.1016/s0891-5849(99)00152-5.


Preischemic hyperglycemia is known to aggravate brain damage resulting from transient ischemia. In the present study, we explored whether this aggravation is preceded by an enhanced formation of reactive oxygen species (ROS) during the early reperfusion period. To that end, normo- and hyperglycemic rats were subjected to 15 min of forebrain ischemia and allowed recovery periods of 5, 15, and 60 min. Sodium salicylate was injected intraperitoneally in a dose of 100 mg/kg, and tissues were sampled during recirculation to allow analyses of salicylic acid (SA) and its hydroxylation products, 2,3- and 2,5-dihydroxybenzoate (DHBA). Tissue sampled from thalamus and caudoputamen in normoglycemic animals failed to show an increase in 2,3- or 2,5-DHBA after 5 and 15 min of recirculation. However, such an increase was observed in the neocortex after 60 min of recirculation, with a suggested increase in the hippocampus as well. Hyperglycemia had three effects. First, it increased 2,5-DHBA in the thalamus and caudoputamen to values exceeding normoglycemic ones after 15 min of recirculation. Second, it increased basal values of 2,5- and total DHBA in the neocortex. Third, it increased the 60-min values for 2,5- and total DHBA in the hippocampus. These results hint that, at least in part, hyperglycemia may aggravate damage by enhancing basal- and ischemia-triggered production of ROS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain Injuries / etiology
  • Brain Injuries / metabolism
  • Brain Ischemia / complications*
  • Brain Ischemia / metabolism*
  • Gentisates*
  • Hydroxybenzoates / metabolism
  • Hydroxyl Radical / metabolism*
  • Hyperglycemia / complications*
  • Hyperglycemia / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Salicylic Acid / metabolism
  • Tissue Distribution


  • Gentisates
  • Hydroxybenzoates
  • Reactive Oxygen Species
  • Hydroxyl Radical
  • 2,3-dihydroxybenzoic acid
  • Salicylic Acid
  • 2,5-dihydroxybenzoic acid