Differential influences of various arsenic compounds on glutathione redox status and antioxidative enzymes in porcine endothelial cells

Abstract.

The cellular response and detoxification mechanisms in porcine endothelial cells (PAECs) to arsenic trioxide (As₂O₃), sodium arsenite (NaAsO₂) and sodium arsenate (Na₂HAsO₄) were investigated. NaAsO₂ at 20 μM for 72 h increased Cu/Zn superoxide dismutase activity resulting in elevated intracellular hydrogen peroxide levels, but As₂O₃ and Na₂HAsO₄ did not. Trivalent arsenic compounds increased intracellular oxidized glutathione (GSSG) and total glutathione (GSH) and cellular glutathione peroxidase (cGPX) and glutathione S-transferase (GST) activity, but not glutathione reductase activity. The increased cGPX activity resulted in an elevated cellular GSSG content. Na₂HAsO₄ increased the cellular GSSG level at 72 h compared to controls. These results imply that the increased GSH content responding to the oxidative stress by trivalent arsenic compounds may be mainly related to the regulation of GSH turnover. The increased GST activity implies that the elevated intracellular GSH level responding to the oxidative stress may be used to conjugate arsenic in PAECs and facilitate arsenic efflux.