Canine myocardial reperfusion injury: protection by a free radical scavenger, N-2-mercaptopropionyl glycine

Oxygen-derived free radicals and their metabolites may contribute to the extension of irreversible cellular injury, which occurs on reperfusion of the previously ischemic myocardium. Therefore, therapy directed against the toxic effects of reactive oxygen species may provide protection to the ischemic myocardium, which undergoes subsequent reperfusion. We evaluated the effectiveness of N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, to limit the extent of irreversible injury resulting from 90 min of ischemia followed by 6 h of reperfusion in a canine model of myocardial infarction. In three groups of dogs, MPG (20 mg/kg) was administered as a constant infusion into the left atrium. Group I received MPG for 2 h, starting 15 min before occlusion of the left circumflex coronary artery and ending 15 min after reperfusion. Group II received MPG for 1 h, starting 15 min before reperfusion. Group III received MPG for 1 h beginning 45 min after reperfusion. Each group was compared with its respective saline control group. Infarct size was reduced by 35% in Group I (32.2 +/- 5.1% vs. 47.7 +/- 3.4% of the area at risk, p less than 0.05) and Group II (31.4 +/- 3.6% vs. 47.5 +/- 5.1% of the area at risk, p less than 0.025) in comparison with the saline treated control animals. In contrast, in Group III infarct size did not differ significantly from the saline-treated control group (45.9 +/- 3.3% vs. 47.7 +/- 3.5% of the area at risk). The percent of left ventricle at risk did not differ among the groups. The beneficial effects of MPG could not be explained on the basis of hemodynamic differences. In addition, MPG did not influence regional myocardial blood flow. In vitro studies indicated that MPG effectively scavanges O2- generated by the hypoxanthine-xanthine oxidase reaction, as well as by PMA-activated polymorphonuclear leukocytes. Based on these observations, we propose that MPG exerts its beneficial effects by protecting against free radical-mediated damage during the early phase of reperfusion.     

Radioprotective effects of exogenous glutathione against whole-body gamma-ray irradiation: age- and gender-related changes in malondialdehyde levels,superoxide dismutase and catalase activities in rat liver

Age- and gender-related changes in malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities in rat livers exposed to different doses of whole-body gamma-ray radiation were determined. In addition, the effects of exogenous glutathione (GSH) against radiation injury in rat livers were investigated. We found that MDA levels have an age-associated increment and an increasing radiation dose-related elevation, although they decrease slightly in the 4 Gy group. The MDA levels in old rats were lower in males than in females, while those of young rats did not change. There were no observed age-related changes in SOD activities, although male rats had higher SOD activity than females. Female rats had the highest CAT activities in the 4 Gy group, while male rats had the highest CAT activities in the 6 Gy group. CAT activities in the 8 Gy group were lower than those of the 2 Gy group for each gender and age. While MDA levels were decreased and CAT activities increased by GSH, SOD activities remained unchanged. The results indicate that gamma-ray radiation affects gender- and age-dependent MDA levels, SOD and CAT activities. Administration of GSH appears to be a useful approach to reduce radiation injury by reducing MDA levels and increasing CAT activities.