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 (CO3•−)-driven tocopherol-mediated human LDL peroxidation (TMP) in vitro and in vivo. CO3•−, generated in vitro by the SOD1/H2O2/bicarbonate system, readily promoted TMP, which was dependent on α-tocopherol and bicarbonate concentrations, and was inhibited by the CO3•− scavenger ethanol; moreover, TMP induced in vitro by the SOD1/H2O2/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, CO3•−-driven LDL TMP in vivo. In conclusion, the present study highlights the occurrence of bicarbonate-dependent, CO3•−-driven human LDL TMP, the role of which in pathological conditions such as atherosclerosis warrants, however, further investigation.