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 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.
Villalobos
M A
MA
Department of Anatomy, School of Medicine, University of Málaga, 29071, Málaga, Spain.
De La Cruz
J P
JP
Cuerda
M A
MA
Ortiz
P
P
Smith-Agreda
J M
JM
Sánchez De La Cuesta
F
F
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology*; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008054:Lipid Peroxides; D013778:Tetrazolium Salts; D017392:Thiobarbituric Acid Reactive Substances; C011314:neotetrazolium; D012436:S-Adenosylmethionine; D005978:Glutathione