Effect of N-acetylcysteine and/or deferoxamine on oxidative stress and hyperactivity in an animal model of mania.
Studies have consistently reported the participation of free radicals in Bipolar Disorder. Administration of d-amphetamine (d-AMPH) is a relevant animal model of mania and it increases oxidative stress in rat brain. Evidences indicate that the antioxidants N-acetylcysteine (NAC) and Deferoxamine (DFX) exert protective effects in the brain. The present study was designed to evaluate the effects of NAC, DFX or their combination on AMPH-induced hyperactivity. The protein oxidation levels were analyzed in prefrontal cortex and hippocampus. In the first animal model (reversal treatment), adult male Wistar rats received saline or d-AMPH for 14 days, and from the 8th to the 14th day, they were treated with saline, NAC, DFX, or NAC plus DFX. In the second animal model (prevention treatment), rats were pretreated with saline or antioxidant regime, and from the 8th to the 14th day, they also received saline or d-AMPH. In the prefrontal cortex, the protein carbonyls were not affected by the treatment with antioxidants alone but it was increased by treatment with NAC plus DFX. At the same model, NAC plus DFX reversed the protein damage in the hippocampus, but NAC alone increased this damage. In the prevention treatment, it was observed that the protein damage in the prefrontal cortex was prevented by DFX or NAC plus DFX. In the hippocampus, the pretreatment with all antioxidant regime prevented protein damage induced by d-AMPH. At both treatments (reversal or prevention) the antioxidants did not present any effect against d-AMPH-induced hyperactivity. In conclusion, NAC or DFX and the combination of NAC plus DFX reverse and protect against d-AMPH-induced oxidative protein damage. Using these protocols we could not observe affects on locomotion, however this effect varies depending on the brain region and the treatment regime.
Valvassori
Samira S
SS
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Petronilho
Fabrícia C
FC
Réus
Gislaine Z
GZ
Steckert
Amanda V
AV
Oliveira
Virgínia B M
VB
Boeck
Carina R
CR
Kapczinski
Flávio
F
Dal-Pizzol
Felipe
F
Quevedo
João
J
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000523:psychology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000517:prevention & control / Q000523:psychology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D016166:Free Radical Scavengers; D003676:Deferoxamine; D003913:Dextroamphetamine; D000111:Acetylcysteine