Rat liver antioxidant response to iron and copper overloads

The rat liver antioxidant response to Fe and Cu overloads (0-60 mg/kg) was studied. Dose- and time-responses were determined and summarized by t(1/2) and C-50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58-66%) and Cu (79-81%) loads, with t(1/2) of 4.0 and 2.0 h. The C-50 were in a similar range for all the indicators (110-124 mu g Fe/g and 40-50 mu g Cu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60-75%; t(1/2): 4.5 and 4.0 h). Lipophilic antioxidants were also decreased (30-92%; t(1/2): 7.0 and 5.5 h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t(1/2): 8-8.5 h and Mn-SOD: t(1/2): 8.5-8.0 h). Catalase activity was increased after Fe (65%; t(1/2): 8.5 h) and decreased after Cu (26%; t(1/2): 8.0 h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22-39% with a t(1/2) of 4.5 h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol ( -SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads. (C) 2014 Elsevier Inc. All rights reserved.