α-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells

Abstract

Both alpha-lipoic acid (LA) and ascorbic acid (vitamin C) have been shown to improve endothelial dysfunction, a precursor of atherosclerosis. Since oxidant stress can cause endothelial dysfunction, we tested the interaction and efficacy of these antioxidants in preventing oxidant damage to lipids due to both intra- and extracellular oxidant stresses in EA.hy926 endothelial cells. LA spared intracellular ascorbate in culture and in response to an intracellular oxidant stress induced by the redox cycling agent menadione. Extracellular oxidant stress generated by incubating cells for 2 h in with 0.2 mg/ml LDL and 5 muM Cu2+ caused a time-dependent increase of the lipid peroxidation product malondialdehyde in both cells and LDL, preceded by rapid disappearance of; alpha-tocopherol in LDL. alpha-Lipoic acid at concentrations of 40-80 microM blunted these effects. Similarly, intracellular ascorbate concentrations of 1-2 mM also prevented Cu2+-induced lipid peroxidation in LDL and cells. Cu2+-dependent oxidation of LDL in the presence of ascorbate-loaded cells decreased intracellular ascorbate by 20%, but this decrease was not reversed by LA. Both LA and ascorbate protect endothelial cells and LDL from either intra- or extracellular oxidant stress, but that LA does not spare ascorbate in oxidatively stressed cells.

Alpha‐lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo‐controlled randomized trial

“…Thus, it might be speculated that ALA might have influenced LDLcholesterol levels. Experimental and clinical studies have shown reduction of (oxidized) LDL by ALA [27,28].…”

Vitamin C in Disease Prevention and Cure: An Overview

“…Study has also shown that when proliferating endothelial cells were treated with AA, increased retinoblastoma protein (Rb) phosphorylation was observed with decreased level of p53 as compared to untreated cells. Furthermore, the addition of AA to TNF-alpha-treated proliferating endothelial cells blocked both the inhibition of retinoblastoma protein phosphorylation and enhanced p53 expression induced by TNF-alpha and TNF-alpha-induced apoptosis [117].…”

“…Further, lipophilic derivatives of AA showed protective effect on lipidperoxide induced endothelial injury [116]. In endothelial cells, AA prevented atherogenic modification of mildly oxidized LDL [110] and preserved a-tocopherol in both cells and LDL [117]. Although AA may not reverse established atherosclerosis, it can prevent the endothelial dysfunction that is the earliest sign of many vascular inflammatory conditions.…”

Inflammation in the vascular bed: Importance of vitamin C

“…Glascott and co-workers (Glascott, Jr. et al, 1996) found that there was no sparing of α-tocopherol by ascorbate in hepatocytes exposed to an oxidant stress generated by allyl alcohol. On the other hand, subsequent studies in diverse cell types showed that ascorbate prevented α-tocopherol loss due to milder oxidant stresses in erythrocytes (May et al, 1998b), hepatocytes , and neuronal cells (Li et al, 2003) In endothelial cells, ascorbate prevented atherogenic modification of mildly oxidized LDL (Martin & Frei, 1997) and preserved α-tocopherol in both cells and LDL (Sabharwal & May, 2008). Despite results of in vitro studies, until recently it had not been demonstrated that ascorbate spares α-tocopherol in either animals or humans under oxidant stress.…”