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Biometals. 2018 May 15. doi: 10.1007/s10534-018-0104-8. [Epub ahead of print]

Iron overload prevents oxidative damage to rat brain after chlorpromazine administration.

Author information

1
Facultad de Farmacia y Bioquímica, Fisicoquímica-IBIMOL, Universidad de Buenos Aires, Junín 956, CAAD1113, Buenos Aires, Argentina.
2
Instituto de Bioquímica y Medicina Molecular (IBIMOL), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
3
Chemistry Department, Hendrix College, Conway, AR, 72032, USA.
4
Facultad de Farmacia y Bioquímica, Fisicoquímica-IBIMOL, Universidad de Buenos Aires, Junín 956, CAAD1113, Buenos Aires, Argentina. susanap@ffyb.uba.ar.
5
Instituto de Bioquímica y Medicina Molecular (IBIMOL), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina. susanap@ffyb.uba.ar.

Abstract

The hypothesis tested is that Fe administration leads to a response in rat brain modulating the effects of later oxidative challenges such as chlorpromazine (CPZ) administration. Either a single dose (acute Fe overload) or 6 doses every second day (sub-chronic Fe overload) of 500 or 50 mg Fe-dextran/kg, respectively, were injected intraperitoneally (ip) to rats. A single dose of 10 mg CPZ/kg was injected ip 8 h after Fe treatment. DNA integrity was evaluated by quantitative PCR, lipid radical (LR·) generation rate by electron paramagnetic resonance (EPR), and catalase (CAT) activity by UV spectrophotometry in isolated brains. The maximum increase in total Fe brain was detected after 6 or 2 h in the acute and sub-chronic Fe overload model, respectively. Mitochondrial and nuclear DNA integrity decreased after acute Fe overload at the time of maximal Fe content; the decrease in DNA integrity was lower after sub-chronic than after acute Fe overload. CPZ administration increased LR· generation rate in control rat brain after 1 and 2 h; however, CPZ administration after acute or sub-chronic Fe overload did not affect LR· generation rate. CPZ treatment did not affect CAT activity after 1-4 h neither in control rats nor in acute Fe-overloaded rats. However, CPZ administration to rats treated sub-chronically with Fe showed increased brain CAT activity after 2 or 4 h, as compared to control values. Fe supplementation prevented brain damage in both acute and sub-chronic models of Fe overload by selectively activating antioxidant pathways.

KEYWORDS:

Antioxidant; Brain; Chlorpromazine; Electron paramagnetic resonance; Fe; Oxidative stress

PMID:
29766365
DOI:
10.1007/s10534-018-0104-8

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