The involvement of copper and iron on biomolecules oxidation and oxidative damage: in vitro and in vivo experimental models of acute toxicity.

FERRAROTTI, NIDIA; MUSACCO SEBIO, ROSARIO; SAPORITO MAGRIÑÁ, CHRISTIAN; TORTI, HORACIO; BOVERIS, ALBERTO; REPETTO, MARISA

Buenos Aires

Congreso; VIII International Congress. Society for Free Radical Biology and Medicine.; 2013

Society for Free Radical Biology and Medicine

Iron (Fe) and copper (Cu) are essential biometals, however they become toxic at elevated tissue concentrations. Aim: to study the involvement of Fe and Cu in the acute oxidative damage to biomolecules in vitro and in vivo. In vitro: Phospholipid liposomes (0.5 mg/ml, phosphatidylcholine/phosphatidylserine, 60/40) were incubated for 60 min at 37 ºC with 25 μM of Fe2+ and Cu2+, and hydrogen peroxide (H2O2, 0-50 μM). Phospholipid oxidation was evaluated. In vivo: Sprague Dawley rats (200 g) received 0-60 mg/kg (ip) FeCl2 and CuSO4. Dose and time-responses were determined for in situ liver chemiluminescence (CL), phospholipid and protein oxidation. The metal doses linearly defined the tissue content of both metals. Liver CL increased 4 and 2 times after Fe and Cu overloads (C50% 110 μg Fe/g and 42 μg Cu/g liver), at 4 h. Phospholipid oxidation increased 4 and 1.8 times, and protein oxidation 1.6 and 1.2 times for Fe and Cu. Increments in liver metal content enhanced the rate of free radical reactions and oxidative damage. A similar chemical mechanism of a free-radical mediated process operate for the effects of both metals, through HO• and RO• generation by a Fenton-like homolytic scission of H2O2 and ROOH.