Protective effect of histidine on iron (II)-induced hydroxyl radical generation in rat hearts.
We investigated the efficacy of histidine on iron (II)-induced hydroxyl radical (.OH) generation in extracellular fluid of the rat myocardium using a flexibly mounted microdialysis technique (O system). Rats were anesthetized and a microdialysis probe was implanted in the left ventricular, followed by infusion of sodium salicylate in Ringer's solution (0.5 nmol/microL/min) to detect the generation .OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Iron (II) clearly produced a concentration-dependent increase in .OH formation. A positive linear correlation between iron (II) and the formation of 2,3-DHBA (R2 = 0.987) was observed. However, histidine (25 mM) was infused through a microdialysis probe; iron (II) failed to increase the 2,3-DHBA formation obtained. To examine the effect of histidine on ischemia-reperfusion of the myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, a marked elevation of the levels of 2,3-DHBA was observed in the heart dialysate. When corresponding experiments were performed with histidine (25 mM)-pretreated animals, histidine prevented the ischemia-reperfusion induced .OH generation trapped as 2,3-DHBA. These results indicate that histidine protects the myocardium against ischemia-reperfusion damage by .OH generation.
Department of Pharmacology, Oita Medical University, Japan.
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Obata
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Aomine
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Yamanaka
D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology
D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D006639:Histidine; C009135:2,3-dihydroxybenzoic acid; D007501:Iron; D012980:Sodium Salicylate