Oxidative Stress and Biochemical Markers of Endothelial Dysfunction and Organ Damage under Conditions of Experimental Nonferrous Metal Intoxication.

Chronic nickel intoxication caused by parenteral nickel chloride administration (0.5 mg/kg of body weight) to Wistar rats led to ROS generation inducing LPO in erythrocyte membranes and homogenates of renal, liver, and myocardial tissue. Superoxide dismutase (SOD) activity was inhibited, while catalase activity and ceruloplasmin concentration increased. LPO and its products disrupted nitric oxide production and reduced its bioavailability, which led to the development of endothelial dysfunction and impaired microcirculatory hemodynamics. At the same time, damage of cytoplasmic membranes of internal organs (kidney, liver, and myocardium) was revealed, which was seen from reduced Na(+), K(+)-ATPase activity in homogenates of these organs and increased serum activity of organ-specific (ALT, AST, and γ-glutamyl transpeptidase) and excretory (alkaline phosphatase) enzymes.