Iron (III) attenuates hydroxyl radical generation accompanying non-enzymatic oxidation of noradrenaline in the rat heart.
The present study examined the effect of iron (III) on the generation of free hydroxyl radicals (*OH) in the extracellular fluid of rat myocardium. The generation of *OH was assessed by infusing sodium salicylate in Ringer's solution (0.5 nmol/microl per min) directly into the myocardium of the anaesthetised rat through a microdialysis probe and measuring the non-enzymatic reaction product 2,3-dihydroxybenzoic acid (DHBA) trapped in the dialysate. Tyramine increased the level of 2,3-DHBA concentration dependently. However, in the presence of iron (III) (50 microM), the effect of tyramine was abolished. When iron (III) (50 microM) was administered to tyramine (1 mM)-pre-treated animals, the tyramine-induced stimulation of noradrenaline did not change, but the level of 2,3-DHBA decreased significantly ( n=6, P<0.05). When desferrioxamine (DES), a strong iron (III) chelator, was administered to tyramine (1 mM)-pre-treated animals, a marked increase in 2,3-DHBA formation was seen. Administration of iron (II) to the DES-pre-treated animals increased 2,3-DHBA markedly compared with the iron (II)-only treated group, with a positive linear correlation between iron (II) concentration and *OH trapped as 2,3-DHBA ( R(2)=0.987). DES can reduce iron (III) and thus markedly increases *OH formation. To examine the effect of iron (III) on ischaemia/reperfusion of the myocardium, the heart was subjected to myocardial ischaemia for 15 min by occlusion of the left anterior descending branch of the coronary artery. On reperfusion, noradrenaline and 2,3-DHBA rose markedly in the heart dialysate. The presence of iron (III) (50 microM) abolished the elevation of 2,3-DHBA. Iron (III) also significantly blunted the rise of serum creatine phosphokinase, an index of myocardial damage. The present study demonstrates that the suppression of *OH formation by iron (III) may play a key role in the cardioprotective effect of iron (III) in the rat heart.
Obata
Toshio
T
Department of Pharmacology, Oita Medical University, Hasama-machi, Oita 879-5593, Japan. tobata@oita-med.ac.jp
Yamanaka
Yasumitsu
Y
D000818:Animals; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000032:analysis / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D005290:Ferric Compounds; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D012980:Sodium Salicylate; D009638:Norepinephrine; D014439:Tyramine