Reversal of Haloperidol-Induced Orofacial Dyskinesia and Neuroinflammation by Isoflavones

Abstract

Schizophrenia is a serious mental illness, and its pharmacological treatment consists in the administration of antipsychotics, such as haloperidol. However, treatment with haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). TD is a movement disorder characterized by involuntary movements, which can be studied in animals. So far, there is no effective treatment for TD and alternatives have been sought. Thus, the objective was to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model. Male Wistars rats were treated with haloperidol (1 mg/ kg/day) and/or isoflavones (80 mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and the locomotor activity. In addition, the levels of pro-inflammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of VCM to the levels of the control group. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α:TNF-a and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1β and TNF-α, but not IL-6. It is believed that the beneficial effect found with this treatment is related to their anti-inflammatory potential and also to the action on estrogen receptors (based on findings in the scientific literature). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotic.

Flavonoids bridging the gut and the brain: Intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration

“…Despite the direct role of the gut-brain axis still has to be fully elucidated, the protective effect of isoflavones, especially genistein, on neuroinflammation has been clearly demonstrated in a number of preclinical models, via mechanisms including inhibition of NF-κB, prostaglandins, proinflammatory cytokines, iNOS, ROS and free radical scavenging activity (for review see [128]). For example, isoflavones administration (80 mg/kg/day) protected from neuroinflammation in a rat model of haloperidol-induced dyskinesia, by reducing the expression of IL-1β and TNF-α [129].…”