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Free Radic Res. 2012 Nov;46(11):1387-92. doi: 10.3109/10715762.2012.719613. Epub 2012 Sep 24.

Bicarbonate-dependent, carbonate radical anion-driven tocopherol-mediated human LDL peroxidation: an in vitro and in vivo study.

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Dipartimento di Medicina e Scienze dell'Invecchiamento, and Centro di Scienze dell'Invecchiamento-Fondazione Università G. d'Annunzio, Chieti, Italy.


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.

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