Minimization of free radical damage by metal catalysis of multivitamin/multimineral supplements

Multivitamin/multimineral complexes are the most common dietary supplements. Unlike minerals in foods that are incorporated in bioorganic structures, minerals in dietary supplements are typically in an inorganic form. These minerals can catalyze the generation of free radicals, thereby oxidizing antioxidants during digestion. Here we examine the ability of a matrix consisting of an amino acid and non-digestible oligosaccharide (AAOS) to blunt metal-catalyzed oxidations. Monitoring of ascorbate radical generated by copper shows that ascorbate is oxidized more slowly with the AAOS matrix than with copper sulfate. Measurement of the rate of oxidation of ascorbic acid and Trolox® by catalytic metals confirmed the ability of AAOS to slow these oxidations. Similar results were observed with iron-catalyzed formation of hydroxyl radicals. When compared to traditional forms of minerals used in supplements, we conclude that the oxidative loss of antioxidants in solution at physiological pH is much slower when AAOS is present

Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension

Pulmonary hypertension (PH) is an incurable condition in humans; driven by pulmonary vascular remodeling partially mediated by epigenetic mechanisms; and leading to right ventricular hypertrophy, failure, and death. We hypothesized that targeting chromatin-modifying histone deacetylases may provide benefit. In this Brief Report we describe case comparison studies using the histone deacetylase inhibitor vorinostat (suberanilohydroxamic acid, 5 mg/kg/day for the first 5 study days) in an established model of severe neonatal bovine PH induced by 14 days of environmental hypoxia. Echocardiographic, hemodynamic, and pharmacokinetic data were obtained in hypoxia-exposed (one each, vorinostat-treated vs. untreated) and normoxic vorinostat-treated control animals (n = 2). Echocardiography detected PH changes by day 4 and severe PH over 14 days of continued hypoxic exposure. RV dysfunction at day 4 was less severe in vorinostat-treated compared to untreated hypoxic calves. Cardioprotective effects were partially maintained following cessation of treatment through the duration of hypoxic exposure, accompanied by hemodynamic evidence suggestive of reduced pulmonary vascular stiffening, and modulated expression of HDAC1 protein and genes involved in RV and pulmonary vascular remodeling and pathological RV hypertrophy. Control calves did not develop PH, nor show adverse cardiac or clinical effects. These results provide novel translation of epigenetic-directed therapy to a large animal severe PH model that recapitulates important features of human disease.</jats:p