Inhibition of lung tissue oxidation during ischemia/reperfusion by 2-mercaptopropionylglycine.
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.
Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
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Ayene
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al-Mehdi
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Fisher
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D008625:Tiopronin / Q000494:pharmacology*
D011506:Proteins; D015117:5,8,11,14-Eicosatetraynoic Acid; C038983:1,3-dimethylthiourea; D008625:Tiopronin; D013890:Thiourea; D003676:Deferoxamine