Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
J Inorg Biochem. 2012 Nov;116:63-9. doi: 10.1016/j.jinorgbio.2012.07.004. Epub 2012 Jul 11.
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.
铁（Fe）和铜（Cu）等过渡金属在低水平时对人体和动物的健康是必需的，而在较高水平时则具有毒性。本研究旨在观察 Fe 和 Cu 引起的雄性 Sprague Dawley 大鼠（200 g）急性肝毒性，采用腹腔注射方式给予大鼠 0-60 mg/kg FeCl2 或 0-30 mg/kg CuSO4，以确定自发原位肝化学发光、磷脂过氧化、蛋白质氧化和脂溶性抗氧化剂的剂量和时间反应。剂量与两种金属的组织含量呈线性关系。Fe 和 Cu 过载后，肝化学发光分别增加了 4 倍和 2 倍，半数最大反应浓度（C50%）分别为 110μgFe/g 和 42μgCu/g 肝，半数最大时间反应（t1/2）分别为 4h 和 4h。磷脂过氧化分别增加了 4 倍和 1.8 倍，C50%分别为 118μg Fe/g 和 45μg Cu/g，t1/2 分别为 7h 和 8h。Fe 引起的蛋白质氧化增加了 1.6 倍，C50%为 113μg Fe/g，Cu 引起的蛋白质氧化增加了 1.2 倍，C50%为 50μg Cu/g，t1/2 分别为 4h 和 5h。Fe 和 Cu 在肝脏中的蓄积加速了自由基反应的速率，导致了氧化损伤。一种类似的自由基介导的过程，通过 Fe 类似物的均裂裂解 H2O2 和 ROOH 形成 HO•和 RO•，似乎是两种金属肝毒性的化学机制。
