Gallic acid induces vascular smooth muscle cell death via hydroxyl radical production

Abstract

In the present study, we investigated whether gallic acid (GA) can induce death in cultured vascular smooth muscle cells (VSMCs), and whether production of the hydroxyl radical (.OH) is involved in the process of GA action. GA killed cultured VSMCs from rat aorta, in a dosc- and time-dependent manner. Cytoplasmic shrinkage and nuclear condensation were observed light microscopically in GA-treated VSMCs, which appeared apoptotic. However, the ultrastructure of the VSMC was not typical of apoptosis: nuclear condensation was not glossy, and the plasma membrane and subccellular organelles were disrupted. Although the VSMC were positive for in situ nick end-labeling (TUNEL). they did not show a DNA ladder pattern on gel electrophoresis and were negative for T aq polymerase-based in situ ligation, which is more specific for apoptosis than TUNEL. Moreover. GA-induced cell death was not prevented by Boc-Asp-fmk (a pan-caspase inhibitor). Production of OH was detected in GA-treated VSMCs using high-performance liquid chromatography with salicylic acid as a trapping agent. Lipid peroxidation was also observed. The production of .OH was inhibited by catalase (CAT) and deferoxamine (DFX), and these treatments completely rescued VSMCs from cell death. In a cell-free system, GA produced .OH in the presence of Fe2+-EDTA, which was quenched by CAT and DFX, suggesting involvement of the Haber-Weiss reaction. Oxidative stress by reactive oxygen species, .OH in particular, is one of the mechanisms of GA-induced death of VSMCs, the mode of which was different from typical apoptosis.

Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways

“…With regard to gallic acid (a myricetin metabolite), which displayed a strong antiproliferative effect on B16F10 and Melan-a, ours results confirm those of Ohno et al (2001) [52] and Qiu et al (2000) [53], who suggested that such effects are due to its hydroxylated aromatic structure and not to the presence of a carboxyl group, because trimethoxybenzoic acid showed no such effect on the inhibition of cell growth.…”

Chitosan gallate as a novel potential polysaccharide antioxidant: an EPR study

“…However, other studies have reported the cytotoxic activity of gallic acid. 37,38 Additionally, gallic acid has been reported to have both pro-oxidant and antioxidant properties. 39 …”

Vascular pro-oxidant effects secondary to the autoxidation of gallic acid in rat aorta

“…This antioxidant effect could prove beneficial to numerous disease states, including cardiovascular disease. However, other studies have highlighted the cytotoxic activity of gallic acid: (a) antitumoral effects via apoptosis in certain tumor cell lines [5,6]; (b) cytotoxicity in vascular smooth muscle cells [7] and hepatocytes [8].…”