Involvement of reactive oxygen species and glutathione in gallic acid-induced human umbilical vein endothelial cell death.

Gallic acid (GA) has various biological effects including apoptosis. In this study, we investigated the effects of GA on human primary umbilical vein endothelial cells (HUVECs) in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH). Treatment with 200 or 400 µM GA inhibited the growth of HUVECs at 24 h and induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψm). GA decreased or increased ROS levels including O2•-. It dose-dependently increased GSH depleted cell numbers. Pan-caspase inhibitor (Z-VAD) did not affect cell growth inhibition, cell death, ROS and GSH levels in GA-treated HUVECs. However, N-acetyl-cysteine (NAC; a well known antioxidant) and L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) enhanced cell growth inhibition, cell death and MMP (∆Ψm) loss in GA-treated HUVECs. NAC decreased general ROS levels in GA-treated HUVECs, but strongly increased O2•- levels in these cells. Both NAC and BSO intensified the GSH depletion of GA-treated HUVECs. In conclusion, GA treatment induced growth inhibition and death of HUVECs. The changes of ROS and GSH levels by NAC and BSO influenced cell growth and death in GA-treated HUVECs.