The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation.
Resveratrol (3,4',5-trihydroxystilbene) is a natural phytoalexin synthesized in response to injury or fungal attack, found in the grape skin and wine, specially red wine. A large number of studies have demonstrated that resveratrol regulates many biological activities, namely protection against atherosclerosis by a set of pharmacological properties, including the antioxidant activity. In this study, we explored the capacity of resveratrol in protecting low density lipoproteins (LDL) against either ferrylmyoglobin- or peroxynitrite-mediated oxidation and the underlying mechanisms of its antioxidant potential. Resveratrol efficiently decreases the accumulation of hydroperoxides in LDL promoted by ferrylmyoglobin, a potent oxidant formed by the reaction of metmyoglobin with hydrogen peroxide, in a concentration-dependent manner, promptly reducing the oxoferryl complex to metmyoglobin. Simultaneously, resveratrol is consumed as detected by the rapid decrease in the characteristic peak at 310 nm, in a similar way to that observed upon its reaction with peroxidase/H2O2, pointing to a mechanism of one-electron oxidation and subsequent resveratrol dimer formation. On the other hand, resveratrol inhibits LDL apoprotein modifications induced by peroxynitrite, another potent oxidant formed by the reaction between superoxide and nitric oxide, as assessed by the decrease in apo-B net charge alterations and in carbonyl groups formation mediated by that oxidant. Resveratrol also interacts with peroxynitrite in a similar way to that observed with laccases, suggesting a mechanism of resveratrol oxidation rather than a nitration one. These mechanisms are discussed. Considering that either ferrylmyoglobin or peroxynitrite are physiologically relevant oxidants implicated in several pathologies, including atherosclerosis, our results certainly contribute to the understanding of the antioxidant action of resveratrol and consequently provide a new approach for the cardiovascular benefits associated with moderate consumption of red wine.
Brito
Paula
P
Laboratório de Bioquímica, Faculdade de Farmácia, Universidade de Coimbra and Centro de Neurociências, Couraça dos Apóstolos, 51, r/c, 3000-295 Coimbra, Portugal.
Almeida
Leonor M
LM
Dinis
Teresa C P
TC
D000975:Antioxidants / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008786:Metmyoglobin / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D000077185:Resveratrol; D013056:Spectrophotometry, Ultraviolet; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D008077:Lipoproteins, LDL; D013267:Stilbenes; C028048:ferrylmyoglobin; D008786:Metmyoglobin; D030421:Peroxynitrous Acid; D000077185:Resveratrol