Nitric oxide, chronic iron and copper overloads and regulation of redox homeostasis in rat liver.

Iron [Fe(II)] and copper [Cu(II)] ions produced liver oxidative stress and damage, and as a consequence, changes in the antioxidant protection. The objective of this work is to evaluate whether control of redox homeostasis in chronic overload of Fe(II) and Cu(II) is associated with nitric oxide (NO) and antioxidant enzymes protection in liver. Male Sprague-Dawley rats of 80-90 g received the standard diet ad libitum and drinking water supplemented with either 1.0 g/L of ferrous chloride (0.1% w/v, n = 24) or 0.5 g/L cupric sulfate (0.05% w/v, n = 24) for 42 days. The activities of the enzymes involved in the control of cellular redox homeostasis, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), were determined by spectrophotometric methods, and NO production was determined by the determination of nitrite levels in liver. Chronic overload with Fe(II) and Cu(II) led to a significant increase of NO production while hampering the activity of NADPH oxidase. Meanwhile, the animals supplemented with Fe(II) showed a decrease in SOD and Gpx activities in liver homogenates with respect to baseline activity after 7 days of treatment, whereas the rats which received Cu(II) showed an increased SOD and catalase activity after 28 and 7 days of chronic overload. Further research is required to understand whether the modulation of the activity of these enzymes upon Cu and Fe overload is involved in a common toxic pathway or may serve to control the steady state of oxidant species related to redox signaling pathways.