title: Bicarbonate-dependent, carbonate radical anion-driven tocopherol-mediated human LDL peroxidation: an in vitro and in vivo study.
abstract: We have here investigated possible occurrence of bicarbonate-dependent, carbonate radical anion (CO(3)(•-))-driven tocopherol-mediated human LDL peroxidation (TMP) in vitro and in vivo. CO(3)(•-), generated in vitro by the SOD1/H(2)O(2)/bicarbonate system, readily promoted TMP, which was dependent on α-tocopherol and bicarbonate concentrations, and was inhibited by the CO(3)(•-) scavenger ethanol; moreover, TMP induced in vitro by the SOD1/H(2)O(2)/bicarbonate system occurred in the presence of α-tocopherol that typically underwent slow oxidative consumption. In the in vivo clinical setting, we showed that, compared to controls, hypertensive patients with diuretic-induced metabolic alkalosis and heightened blood bicarbonate concentration had lipid hydroperoxide burden and decreased α-tocopherol content in the LDL fraction, with direct significant correlation between the LDL levels of α-tocopherol and those of lipid hydroperoxides; remarkably, after resolution of metabolic alkalosis, together with normalization of blood bicarbonate concentration, the LDL content of lipid hydroperoxides was decreased and that of α-tocopherol augmented significantly. These findings suggest bicarbonate-dependent, CO(3)(•-)-driven LDL TMP in vivo. In conclusion, the present study highlights the occurrence of bicarbonate-dependent, CO(3)(•-)-driven human LDL TMP, the role of which in pathological conditions such as atherosclerosis warrants, however, further investigation.
authors.affiliation: Dipartimento di Medicina e Scienze dell'Invecchiamento, and Centro di Scienze dell'Invecchiamento-Fondazione Università G. d'Annunzio, Chieti, Italy. dlapenna@unich.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Lapenna
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ciofani
authors.forename: Chiara
authors.initials: C
authors.lastname: Cuccurullo
authors.forename: Matteo
authors.initials: M
authors.lastname: Neri
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Giamberardino
authors.forename: Franco
authors.initials: F
authors.lastname: Cuccurullo
mesh_terms: D001639:Bicarbonates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002254:Carbonates / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014810:Vitamin E / Q000378:metabolism* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001639:Bicarbonates; D002254:Carbonates; D005609:Free Radicals; D008077:Lipoproteins, LDL; C000606290:SOD1 protein, human; D014810:Vitamin E; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D024502:alpha-Tocopherol