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

Abstract

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 (C50%) of 110 μg Fe/g and 42 μg Cu/g liver, and with half maximal time responses (t1/2) of 4 h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C50% of 118 μg Fe/g and 45 μg Cu/g and with t1/2 of 7 h and 8 h. Protein oxidation increased 1.6 times for Fe with C50% at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t1/2 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• and RO• by a Fenton-like homolytic scission of H2O2 and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.