Iron overload prevents oxidative damage to rat brain after chlorpromazine administration

PUNTARULO, SUSANA; CARO, ANDRES A.; PILONI, NATACHA E.

BIOMETALS

SPRINGER

Lugar: Berlin; Año: 2018

0966-0844

The hypothesis tested is that Fe administrationleads to a response in rat brain modulating theeffects of later oxidative challenges such as chlorpromazine(CPZ) administration. Either a single dose(acute Fe overload) or 6 doses every second day (subchronicFe overload) of 500 or 50 mg Fe-dextran/kg,respectively, were injected intraperitoneally (ip) torats. A single dose of 10 mg CPZ/kg was injected ip8 h after Fe treatment. DNA integrity was evaluatedby quantitative PCR, lipid radical (LR) generationrate by electron paramagnetic resonance (EPR), andcatalase (CAT) activity by UV spectrophotometry inisolated brains. The maximum increase in total Febrain was detected after 6 or 2 h in the acute and subchronicFe overload model, respectively. Mitochondrialand nuclear DNA integrity decreased after acuteFe overload at the time of maximal Fe content; thedecrease in DNA integrity was lower after sub-chronicthan after acute Fe overload. CPZ administrationincreased LR generation rate in control rat brain after1 and 2 h; however, CPZ administration after acute orsub-chronic Fe overload did not affect LR generationrate. CPZ treatment did not affect CAT activity after1?4 h neither in control rats nor in acute Fe-overloadedrats. However, CPZ administration to ratstreated sub-chronically with Fe showed increasedbrain CAT activity after 2 or 4 h, as compared tocontrol values. Fe supplementation prevented braindamage in both acute and sub-chronic models of Feoverload by selectively activating antioxidantpathways.