The acute toxicity of iron and copper: Biomolecule oxidation and oxidative damage in rat liver

The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g) that received ip 0-60 mg/kg FeCl2 or 0-30 mg/kg CuSO4. Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C-50%) of 110 mu g Fe/g and 42 mu g Cu/g liver, and with half maximal time responses (t(1/2)) of 4 h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C-50% of 118 mu g Fe/g and 45 mu g Cu/g and with t(1/2) of 7 h and 8 h. Protein oxidation increased 1.6 times for Fe with C-50% at 113 mu g Fe/g and 1.2 times for Cu with 50 mu g Cu/g and t(1/2) of 4 h and 5 h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical-mediated process, through the formation HO center dot and RO center dot by a Fenton-like homolytic scission of H2O2 and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals. (c) 2012 Elsevier Inc. All rights reserved.