Effect of S-adenosyl-L-methionine on rat brain oxidative stress damage in a combined model of permanent focal ischemia and global ischemia-reperfusion

We analyzed the effects of S-adenosyl-L-methionine (SAM) on tissue oxidativ e status in a combined model of permanent focal ischemia and global reperfu sion in the rat brain. The production of thiobarbituric acid reactive subst ances (TBARS) was measured under basal conditions and after induction with ferrous salt as an indicator of brain lipid peroxidation. Total, oxidized a nd reduced glutathione were measured as indicators of the antioxidant defen se capacity of brain tissue. Mitochondrial reduction of tetraphenyl tetrazo lium (TPT) was quantified morphometrically. Results obtained in vitro showe d that incubation with SAM reduced lipid peroxidation, with a maximum inhib ition of 65.12+/-5.99% after incubation with I mmol/l; glutathione producti on was not significantly modified. fn the brain ischemia-reperfusion model, TBARS production increased and glutathione content decreased, and mitochon drial reduction of TPT decreased significantly after ischemia-reperfusion i n areas dependent on carotid circulation. The administration of 50 mg/kg SA M per day for 3 days led to the inhibition of brain lipid peroxidation and increased total glutathione production. These changes were accompanied by a n increase in mitochondrial capacity to reduce TPT. We conclude that SAM re duces oxidative damage in the rat brain in an experimental model of ischemi a-reperfusion. (C) 2000 Elsevier Science B.V. All rights reserved.