title: Intravenous low redox potential saline attenuates FeCl3-induced vascular dysfunction via downregulation of endothelial H2O2, CX3CL1, intercellular adhesion molecule-1, and p53 expression.
abstract: 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 FeCl(3)-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 H(2)O(2) scavenging activity compared with distilled-water-made solutions. The RW-culture medium significantly depressed TNF-α-enhanced endothelial H(2)O(2) 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 FeCl(3)-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. FeCl(3) 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.
authors.affiliation: Department of Internal Medicine, Taipei City Hospital, Chung-Hsiao Branch, Taipei, Taiwan.
authors.forename: Da-Lung
authors.initials: DL
authors.lastname: Chen
authors.forename: Tzen-Wen
authors.initials: TW
authors.lastname: Chen
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.forename: Ping-Chia
authors.initials: PC
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism; D002712:Chlorides; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005290:Ferric Compounds; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007260:Infusion Pumps; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D057772:Vascular System Injuries / Q000139:chemically induced*
chemical_list: D054428:Chemokine CX3CL1; D002712:Chlorides; D005290:Ferric Compounds; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D018799:Intercellular Adhesion Molecule-1; D012965:Sodium Chloride; D006861:Hydrogen Peroxide; C024555:ferric chloride