Possible mechanism of inhibition of nitrite-induced oxidation of oxyhemoglobin by ergothioneine and uric acid.
The time course of oxyhemoglobin oxidation by nitrite consisted of a kinetic lag followed by a transition phase which progressed into a rapid autocatalytic phase. The imidazolthione and imidazolone derivatives, ergothioneine and uric acid, respectively, caused an increase in the duration of the lag phase in a concentration-dependent manner, without affecting the onset and rate of the autocatalytic phase. Neither compound reacted with H2O2 or nitrite, oxidizing species required in the initiation steps of oxyhemoglobin oxidation. On the other hand, both compounds reduced effectively and at comparable rates the high oxidation state of hemoglobin, i.e., ferrylhemoglobin, which is an intermediate species occurring in the autocatalytic phase. In addition, the rate of ergothioneine oxidation, upon its reaction with ferrylmyoglobin, was accelerated by nitrite, thus suggesting a reaction between the thione and nitrogen dioxide. Nitrogen oxide and ferrylhemoglobin are key species in the free radical chain propagation leading to oxyhemoglobin oxidation by nitrite. These data support the view that ergothioneine and urate delay oxyhemoglobin oxidation by nitrite upon the temporary removal of the propagating species, i.e., nitrogen dioxide and, secondarily, ferrylhemoglobin, and within a mechanism encompassing alterations of the nitrite in equilibrium with nitrogen dioxide and ferrylhemoglobin in equilibrium with methemoglobin redox transitions.
Arduini
A
A
Istituto di Scienze, Università degli Studi G. D'Annunzio, Chieti, Italy.
Mancinelli
G
G
Radatti
G L
GL
Hochstein
P
P
Cadenas
E
E
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004880:Ergothioneine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009573:Nitrites / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000378:metabolism*; D013053:Spectrophotometry; D014527:Uric Acid / Q000494:pharmacology*
D009573:Nitrites; D010108:Oxyhemoglobins; D014527:Uric Acid; D004880:Ergothioneine