High Intakes of Bioavailable Phosphate May Promote Systemic Oxidative Stress and Vascular Calcification by Boosting Mitochondrial Membrane Potential-Is Good Magnesium Status an Antidote?

Chronic kidney disease is characterized by markedly increased risk for cardiovascular mortality, vascular calcification, and ventricular hypertrophy, and is associated with increased systemic oxidative stress. Hyperphosphatemia, reflecting diminished glomerular phosphate (Pi) clearance, coupled with a compensatory increase in fibroblast growth factor 23 (FGF23) secretion are thought to be key mediators of this risk. Elevated serum and dietary Pi and elevated plasma FGF23 are associated with increased cardiovascular and total mortality in people with normal baseline renal function. FGF23 may mediate some of this risk by promoting cardiac hypertrophy via activation of fibroblast growth factor receptor 4 on cardiomyocytes. Elevated serum Pi can also cause a profound increase in systemic oxidative stress, and this may reflect the ability of Pi to act directly on mitochondria to boost membrane potential and thereby increase respiratory chain superoxide production. Moreover, elevated FGF23 likewise induces oxidative stress in vascular endothelium via activation of NADPH oxidase complexes. In vitro exposure of vascular smooth muscle cells to elevated Pi provokes an osteoblastic phenotypic transition that is mediated by increased mitochondrial oxidant production; this is offset dose-dependently by increased exposure to magnesium (Mg). In vivo, dietary Mg is protective in rodent models of vascular calcification. It is proposed that increased intracellular Mg opposes Pi's ability to increase mitochondrial membrane potential; this model could explain its utility for prevention of vascular calcification and predicts that Mg may have a more global protective impact with regard to the direct pathogenic effects of hyperphosphatemia.

Solvent effects on phytochemical constituent profiles and antioxidant activities, using four different extraction formulations for analysis of Bucida buceras L. and Phoradendron californicum.

BACKGROUND: The present investigation evaluated 4 different solvent compositions for their relative capacity to extract total phenolic and total flavonoid (TF) components of the leaves, trunks, and stems of Bucida buceras L. (Combretaceae), and the stems of Phoradendron californicum (Viscaceae), plus mesquite and oak species endemic to the Southwestern United States, northern Mexico, and tropical regions of Central and South America, as well as to profile the composition of these plant materials and to measure their antioxidant capacity. METHODS: The total phenolic content of plant material used in the present investigation was measured using the Folin-Ciocalteau assay. Total flavonoids were assayed by AlCl3 and 2,4-dinitrophenylhydrazin colorimetry. Nitroblue tetrazolium was utilized for scavenging of superoxide anion, and in vitro antioxidant activity was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl and Ferric Reducing/Antioxidant Power assays. RESULTS: Phytochemical screening of each plant extract evaluated revealed the following major results: (1) No evidence of alkaloids for each of the extraction phases tested was detected in the hexanic, ethanolic, or aqueous phases of Bucida buceras and Phoradendron californicum (oak and mesquite); (2) Analysis of the hexane phase of B. buceras and P. californicum (mesquite) extracts revealed the presence of carotenes, triterpenes/steroids, and lactonic groups; (3) Analysis of the ethanol and aqueous extraction phases for both plants revealed the presence of a diverse range of compounds, including tripterpenes/steroids, lactonics groups, saponins, phenols/tannins, amines and/or amino acids, and flavonoids/anthocyanins; and (4) The highest total phenolic and flavonoid content were observed in P. californicum (oak): 523.886 ± 51.457 µg GAE/mg extract and 409.651 ± 23.091 µg/mg of extract for methanol and aqueous fractions, respectively. The highest flavonoid content was 237.273 ± 21.250 µg PNE/mg extract in the acetone extract of Bucida buceras stems; while the flavonol content (260.685 ± 23.031 µg CE/mg extract) was higher in the ethanol extract of P. californicum (oak). The acetone extract of B. buceras trunk extract showed the highest levels of DPPH radical-scavenging activity (IC50 = 4.136 ± 0.446 µg/mL) and reducing power (4928.392 ± 281.427 µM AAE/mg extract). The highest superoxide radical scavenging activity (IC50) was 55.249 ± 9.829 µg/mL, observed in acetone extracts of B. buceras leaves. CONCLUSIONS: The results of the present investigation demonstrated the effects of extraction solvent on phenolic and flavonoid content yield-and antioxidant activities by Bucida buceras and Phoradendron californicum. The present investigation further revealed that Bucida buceras exhibited optimal antioxidant capacity when acetone was used as extraction solvent; and the highest yield of phenols and flavonoids were obtained from the P. californicum oak, using methanol and aqueous solvents, respectively.