Protective Effect of Dinitrosyl Iron Complexes Bound with Hemoglobin on Oxidative Modification by Peroxynitrite

Area of Science:

• Biochemistry
• Physiology

Background:

• Dinitrosyl iron complexes (DNICs) are physiological nitric oxide (NO) carriers.
• DNICs exhibit antioxidant and antiradical properties.
• The protective mechanisms of hemoglobin-bound DNICs (Hb-DNICs) against peroxynitrite-induced oxidative damage are not well understood.

Purpose of the Study:

• To investigate the protective effects of Hb-DNICs against peroxynitrite-mediated oxidative modification of hemoglobin.
• To elucidate the mechanisms underlying Hb-DNIC protection.

Main Methods:

• Electron paramagnetic resonance (EPR) spectroscopy was used to monitor Hb-DNICs and oxidative damage.
• Analysis of amino acid residue oxidation (tryptophan, tyrosine), carbonyl derivative formation, protein crosslinking, and heme degradation.

Main Results:

• Hb-DNICs are dose-dependently destroyed by peroxynitrite.
• DNICs effectively inhibit the oxidation of tryptophan and tyrosine residues.
• DNICs prevent the formation of carbonyl derivatives, inter-subunit crosslinks, and heme degradation.
• These protective effects may involve the reduction of the oxoferryl heme form and direct interception of peroxynitrite and radicals.

Conclusions:

• Hb-DNICs offer significant protection against peroxynitrite-induced oxidative damage to hemoglobin.
• DNICs' ability to scavenge radicals and reduce oxidized heme contributes to their protective role.
• These findings suggest a potential therapeutic role for DNICs in preventing myocardial ischemia.