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Arch Biochem Biophys. 1993 Jun;303(2):307-12.

Inhibition of lung tissue oxidation during ischemia/reperfusion by 2-mercaptopropionylglycine.

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Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.


The effect of 2-mercaptopropionylglycine (MPG), a potent free radical scavenger, on ischemia/reperfusion-induced tissue oxidation in isolated perfused rat lung was investigated. The isolated lung, continuously ventilated with 95% oxygen, was subjected to 1 h global ischemia followed by 1 h reperfusion with or without the presence of an antioxidant. In ischemic/reperfused lungs, there was a significant increase in protein oxidation (carbonyl formation) and lipid peroxidation (thiobarbituric acid reactive substances) to 10.7 nmol/mg protein and 176 pmol/mg protein, respectively, at the end of reperfusion. MPG administered at 6 mg/kg body wt intravenously to the rats prior to isolation of lung reduced protein oxidation by 65% and lipid peroxidation by 40%. An additional effect was noted when MPG was also added to the perfusate (0.275 mg/ml) during reperfusion. Pretreatment with dimethylthiourea (DMTU) or addition of desferal to the perfusate also significantly reduced the protein oxidation of lung ischemia/reperfusion. The addition of DMTU or desferal with MPG showed no additive effect. However, eicosatetraynoic acid (100 microM), a cyclooxygenase and lipoxygenase inhibitor, added with MPG reduced ischemia/reperfusion-induced lipid peroxidation by 80%, which was significantly greater than the protective effect exhibited by MPG alone. The oxidative stress on the lung tissue components was also demonstrated by a decrease in the sulfhydryl content of "end ischemic" lungs; MPG pretreatment maintained the sulfhydryl level at the control level in ischemic lungs. The results indicate that MPG at relatively low and non-toxic concentrations can markedly inhibit the oxidation of tissue sulfhydryls, soluble protein, and lipids associated with ischemia/reperfusion injury of the lung.

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