Time and dose profile of clinical symptoms, mitochondrial dysfunction and oxidative damage by copper toxicity in rat liver.

ACOSTA, JM; MUSACCO SEBIO, R; SAPORITO MAGRIÑÁ, CHRISTIAN; TUTTOLOMONDO, MV; DESIMONE, M; BOVERIS, A; REPETTO, M

Mar del Plata, Buenos Aires

Congreso; LXI Reunión anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Acute copper (Cu) toxicity depends on the dose and time of Cu exposition. At dose of 5 mg Cu/kg, 100% of the animals survive for 48 h without clinical symptoms of Cu toxicity, but with oxidative damage to liver phospholipids and proteins. Nevertheless, with doses between 6 and 7 mg Cu/kg, 75% of rats survive for 6 h, and higher than 7.5 mg Cu/kg, 75 to 100% of rat death, one hour after treatment, with severe clinical symptoms of Cu toxicity. Hypothesis: The oxidative damage and death by acute toxicity of Cu is related to progressive mitochondrial dysfunction in liver. Objective: to evaluate whether oxidative damage, clinical symptoms and death by Cu toxicity in rat liver are associated to mitochondrial dysfunction. Methodology: Oxidative damage was evaluated in liver of male Sprague Dawley rats (200 g) at different doses and times from overload Cu (5-10 mg Cu/kg, ip, and at 1 and 6 h), by measuring in cytosol and mitochondria, the oxidation of phospholipids (TBARS) and superoxide dismutase activity (SOD) (Cu,Zn-SOD: SOD1); and mitochondrial function, by measuring the oxygen consumption (ΔO2) in liver isolated mitochondria with an electrode type Clark. Results: With dose of 6.5 mg Cu/kg, TBARS increased 100% in liver cytosol with clinical symptoms and died at 1.5 h (C:0.24 ± 0.02 nmol/mg protein, p