Intravenous low redox potential saline attenuates FeCl₃-induced vascular dysfunction via downregulation of endothelial H₂O ₂, CX3CL1, intercellular adhesion molecule-1, and p53 expression

Exaggerated reactive oxygen species (ROS) may contribute to vascular injury by the enhancement of CX3CL1, intercellular adhesion molecule-1 (ICAM-1), and pro-apoptotic p53 expression. Reduced water with safely antioxidant activity may protect vascular tissue against oxidative injury. We established reduced water (RW) by using a modified magnesium alloy and evaluated the effects of an RW-made culture medium on TNF-α-induced endothelial damage in vitro and intravenous RW-made saline (0.9%NaCl) infusion on FeCl₃-induced arterial injury in rats in vivo. Several oxidative stresses were evaluated by using a chemiluminescence analyzer, Western blot, and immunohistochemistry. We found that the established RW, RW-culture medium, and RW saline displayed a lower redox potential (<-150 mV) and efficient H₂O₂ scavenging activity compared with distilled-water-made solutions. The RW-culture medium significantly depressed TNF-α-enhanced endothelial H ₂O₂ production; improved CX3CL1, ICAM-1, and p53 expression; and inhibited activated monocyte adhesion to endothelial cells as well as to the CX3CL1 or the ICAM-1 coated plate when compared with the distilled-water-culture medium. In the in vivo study, the time required for FeCl₃-induced occlusion in the urethane anesthetized rat's carotid and femoral arteries was significantly extended by intravenous RW saline infusion compared with distilled-water saline. FeCl₃ stimulation significantly enhanced vascular NADPH oxidase activity, ROS production, as well as CX3CL1, ICAM-1, p53, 3-nitrotyrosine, and 4-hydroxynonenal expression in the damaged arteries. Intravenous RW saline significantly reduced all the FeCl ₃-enhanced oxidative parameters when compared with intravenous distilled-water-saline infusion. We conclude that the RW-culture medium and saline made from magnesium alloy confer cardiovascular protection by the antioxidant capability.