Injury, have been administered in patients with AMI [50]. Although the scientific
Injury, have been administered in patients with AMI [50]. Although the scientific rationale, epidemiologic data, and retrospective studies have been persuasive, prospective, randomized, placebo-controlled trials have so far failed to verify the actual benefit of antioxidant vitamins in human diseases [51-54]. Among the possible contributory factors likely to account for this discrepancy,the lack of consideration of basic aspects, such as the pharmacokinetic properties of antioxidant vitamins, will be discussed later. In agreement with this view, previous attempts to reduce free PM01183MedChemExpress Lurbinectedin radical production after PCA for AMI by oral administration of vitamin C, failed to attenuate the increased production of F2-isoprostanes [55]. In turn, Jaxa-Chamiec et al. [56], performing a randomized, double-blind, placebo-controlled multicentric study in 800 patients, analyzed the effects of combined vitamins C and E, through infusion and capsules, could not demonstrate a major effect of this antioxidant treatment on the clinical outcome of patients, although diabetes patients showed a reduction in 30-day cardiac mortality [57]. It should be noted that the authors recognize as a limitation of the study the fact that the dose of vitamin C used in the study increases its plasma levels only up to 0.1 mM, a concentration 100 times lower than that required to scavenge superoxide anion. Vitamin E, mainly -tocopherol, is the major peroxyl radical scavenger in biologic lipid phases such as membranes or LDL [58,59]. The antioxidant action has been ascribed to its ability PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28499442 to act chemically as a lipid-based free radical chain-breaking molecule, thereby inhibiting lipid peroxidation through its own conversion into an oxidized product, -tocopheroxyl. -Tocopherol can be restored by reduction of the -tocopheroxyl radical with redox-active reagents like vitamin C or ubiquinol [60]. In clinical studies of ischemia-reperfusion injury, positive effects of a multivitamin antioxidant solution, including vitamin E, were described for revascularization of the lower extremities, kidney transplantation, liver surgery, and aortic aneurysm repair [61-64]. Preoperative administration of vitamin E is safe, and it may have beneficialeffects by reducing the impact of ischemia-reperfusion injury in liver surgery [65]. However, homologous studies in AMI are still lacking. Regarding vitamin C, intraarterial administration of high doses of ascorbate has been demonstrated to abolish the in vivo effects of superoxide anion in the impairment of vascular endothelial function in subjects with essential hypertension [66]. In addition, recent in vitro studies have also been successful to study the effects of oxidative stress with and without this vitamin C concentration, thus validating the use of this concentration of ascorbate to counteract the effects of oxidative stress [66]. Vitamin C concentration in plasma is tightly controlled, and excess of vitamin C is excreted as a function of dose, being completely saturated at doses of 400 mg daily and higher, producing a steady-state plasma concentration of approximately 80 M [67]. Unfortunately, this concentration is not enough to scavenge superoxide anion. Therefore, in settings accompanied by oxidative stress, such as the myocardial ischemiareperfusion cycle, a beneficial effect of oral administration of vitamin C in the prevention of oxidative damage should not be expected; however, intravenous infusion could be considered with this purpose. Indeed.
