Haloperidol-Loaded Chitosan Nanocompounds Improve Brain Oxidative Stress Markers and Decrease its Adverse Motor Side-Effects in Male Rats.

Abstract

The therapeutic effects of Haloperidol (HP), a classic antipsychotic drug, are accompanied by severe extrapyramidal side effects, resulting in movement disorders in patients. Our aim was to verify the influence of HP carboxymethyl chitosan nanoparticles on the brain functions of HP treated rats. For such, 36 adult male Wister rats were divided into six groups: the first control treated with 2ml saline/kg bwt/day, the second control treated 2ml/kg bwt of (0.2 mg nanoparticle/ml)/day, HP low dose treated with 0.3mg/kg bwt /day, HP high dose treated with 1 mg/kg bwt /day, HP low dose-nano treated with the same low dose loaded on the nanoparticles, and HP high dose- nano treated with the same high dose loaded on the nanoparticles. All the treated groups administered intraperitoneal for 21 consecutive days. Two days before the last dose, locomotors activity was assessed in open field test and catalepsy. At the end of the experiment, the following parameters were determined in the brain of all rats groups: malondialdhyde (MDA), total nitric oxide (TNO), reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio besides 8-hydroxy-2-guanisine (8-hdg), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents in the cortex and striatum. However, the neuroleptic effect of HP was completely improved by haloperidol loaded with nanoparticles by decreasing the neurotoxicity via lowering lipid peroxidation, TNO contents and increasing antioxidant biomarkers in the cortex and striatum of the treated brains. In conclusion, our study suggests that haloperidol loaded with nanoparticles could be suitable choice for treatment of schizophrenia for long time.