neotetrazolium and Reperfusion-Injury

We analyzed the effects of S-adenosyl-L-methionine (SAM) on tissue oxidative status in a combined model of permanent focal ischemia and global reperfusion in the rat brain. The production of thiobarbituric acid reactive substances (TBARS) was measured under basal conditions and after induction with ferrous salt as an indicator of brain lipid peroxidation. Total, oxidized and reduced glutathione were measured as indicators of the antioxidant defense capacity of brain tissue. Mitochondrial reduction of tetraphenyl tetrazolium (TPT) was quantified morphometrically. Results obtained in vitro showed that incubation with SAM reduced lipid peroxidation, with a maximum inhibition of 65.12+/-5.99% after incubation with 1 mmol/l; glutathione production was not significantly modified. In the brain ischemia-reperfusion model, TBARS production increased and glutathione content decreased, and mitochondrial reduction of TPT decreased significantly after ischemia-reperfusion in areas dependent on carotid circulation. The administration of 50 mg/kg SAM per day for 3 days led to the inhibition of brain lipid peroxidation and increased total glutathione production. These changes were accompanied by an increase in mitochondrial capacity to reduce TPT. We conclude that SAM reduces oxidative damage in the rat brain in an experimental model of ischemia-reperfusion.

Topics: Animals; Brain; Brain Ischemia; Glutathione; Lipid Peroxides; Male; Mitochondria; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; S-Adenosylmethionine; Tetrazolium Salts; Thiobarbituric Acid Reactive Substances

The effects of pyrimido-pyrimidine derivatives (dipyridamole, RA-642 and mopydamole) on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The antiperoxidative effect of RA-642 (in the microM range) was 10 times more potent than that of dipyridamole. Mopydamole did not exert any inhibitory effect on MDA production. In a model of ischemia reperfusion with bilateral occlusion of the common carotid arteries for 1 h and restoration of circulation for a period of 2 h, dipyridamole inhibited FeAs-induced MDA production but did not protect from postischemic brain tissue damage (measured by mitochondrial reduction of tetraphenyl tetrazolium). RA-642 inhibited FeAs-induced MDA production and showed 50-67% protection from tissue damage as compared with untreated animals, while mopydamole did not inhibit MDA production and showed 30-48% protection. No correlation was found between inhibition of lipid peroxidation and protection from brain tissue damage.

Topics: Animals; Brain; Dipyridamole; Disease Models, Animal; Ischemic Attack, Transient; Lipid Peroxidation; Male; Mitochondria; Mopidamol; Oxidation-Reduction; Pyrimidines; Rats; Rats, Wistar; Reperfusion Injury; Tetrazolium Salts