Iron overload and chlorpromazine effect on oxidative stress in brain

PUNTARULO S; PILONI NE

Mar del Plata

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

Schizophrenia and other psychotic disorders are widely treated with chlorpromazine (CPZ), which is frequently associated with several adverse side effects like metabolic disorders due to changes in lipid and glucose metabolism. Oxidative stress triggered by Fe overload was recently reported to be followed by beneficial responses, that were described as an hormetic effect. Fe administration pattern is a critical factor to determine the type of alterations to the cellular oxidative metabolism observed. The hypothesis tested here was that the pattern of administration of Fe affects the response to CPZ in the rat brain. Male Sprague-Dawley rats (180 ± 10 g) were used. In the acute Fe overload, a single dose of 500 mg Fe-dextran /kg was intraperitoneally (ip) injected. In the subchronic Fe overload, 6 doses of 50 mg Fe-dextran /kg was ip injected every second day. In both protocols, control rats were sham-injected ip with saline solution. At 8 h after the single or the 6th dose in the acute and subchronic Fe treatment, respectively, a single dose of 10 mg CPZ/kg was ip injected. At specific time points after CPZ treatment (1, 2 and 4 h), brain was removed. Lipid radical (LR●) generation rate, determined by Electron Paramagnetic Resonance (EPR), was increased at 1 and 2 h post administration of CPZ, and returned to control values at 4 h. Catalase (CAT) activity, assayed spectrophotometrically, was no affected by CPZ administration. After acute and subchronic Fe treatment, a single dose of CPZ did not lead to modifications in LR● generation rate from 1 to 4 h post CPZ administration. However, after acute Fe overload, CAT activity was not modificated by CPZ administration, but after subchronic Fe treatment, a single dose of CPZ lead to an increase in CAT activity at 2 and 4 post administration. These results suggest that the hermetic effect is triggered by Fe overload by both administrations protocols, nevertheless it seems that the mechanisms are different.