title: 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 FeCl(2) or 0-30 mg/kg CuSO(4). 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 μgFe/g and 42 μgCu/g liver, and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C(50%) of 118 μg Fe/g and 45 μg Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C(50%) at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t(1/2) of 4h and 5h 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 H(2)O(2) and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.
authors.affiliation: Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
authors.forename: Alberto
authors.initials: A
authors.lastname: Boveris
authors.forename: Rosario
authors.initials: R
authors.lastname: Musacco-Sebio
authors.forename: Nidia
authors.initials: N
authors.lastname: Ferrarotti
authors.forename: Christian
authors.initials: C
authors.lastname: Saporito-Magriñá
authors.forename: Horacio
authors.initials: H
authors.lastname: Torti
authors.forename: Francisco
authors.initials: F
authors.lastname: Massot
authors.forename: Marisa G
authors.initials: MG
authors.lastname: Repetto
mesh_terms: D000818:Animals; D003300:Copper / Q000633:toxicity*; D006207:Half-Life; D007501:Iron / Q000633:toxicity*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D049449:Luminescence; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003300:Copper; D007501:Iron