Avaliação dos efeitos antioxidantes e neuroprotetores da naringenina em modelo de discinesia orofacial induzida por haloperidol em ratos

Abstract

Tardive dyskinesia (TD) is a persistent hyperkinetic movement disorder, generally irreversible, consequence of the use of dopamine receptor blocking agents, including antipsychotic drugs. Although the recent development of two drugs approved for the treatment of DT, they have adverse effects and are still considered very expensive. Despite substantial progress, more work needs to be done concerning the potential for TD prevention. Based on that, the study aims to evaluate the potential neuroprotective role of the antioxidant naringenin in a model of orofacial dyskinesia (OD), induced by haloperidol, in male Wistar rats. Animals were selected into 5 groups: 1- control; 2- haloperidol 1mg/kg; 3- haloperidol 1mg/kg + naringenin 10mg/kg; 4- haloperidol 1mg/kg + naringenin 25mg/kg; 5- haloperidol 1mg/kg + naringenin 50mg/kg. The treatment was carried out for 21 days and the behavioural tests weekly (7, 14 and 22 days). Behavioural parameters were evaluated, including number of vacuous chewing movements (VCMs) (assessment of orofacial movements), locomotor activity (narrow beam and open field), motor coordination (rotarod) and memory test (ymaze). On the 22nd day, the brain areas (hippocampus, prefrontal cortex and striatum) were removed for the determination of TBARS, nitrite, glutathione, TNF-α and IL-1β levels. Haloperidol treatment altered all parameters in behavioral tests, increasing VCMs, reducing locomotor activity, motor coordination and memory of the rats. In addition, increased oxidative stress, reduced endogenous antioxidant and increased proinflammatory cytokines. Coadministration of naringenin improved behavioural alterations and reduced lipid peroxidation and cytokines levels, showing a promising role in the prevention of OD induced by typical antipsychotics