Reversal of haloperidol-induced orofacial dyskinesia and neuroinflammation by isoflavones.

BACKGROUND: Schizophrenia is a mental illness and its pharmacological treatment consists in the administration of antipsychotics like haloperidol. However, haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). So far, there is no effective treatment against TD and alternatives for it have been sought. Isoflafones have been studied as neuroprotector and inhibitor of monoamine oxidase enzyme. Thus, the objective is to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model. METHODS AND RESULTS: Male Wistar 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 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. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1ß:IL-1ß, tumor necrosis factor-α: TNF-α and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1ß and TNF-α, but not IL-6. CONCLUSIONS: It is believed that the beneficial effect found with this alternative treatment is related to its anti-inflammatory potential and to the action on estrogen receptors (based on scientific literature findings). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotics.

Sporothrix brasiliensis produces the highest levels of oxidative stress in a murine model among the species of the Sporothrix schenckii complex

Abstract INTRODUCTION: We compared indicators of oxidative stress in the tissue of mice infected with strains from Sporothrix schenckii complex. METHODS: Mice were inoculated with Sporothrix brasiliensis, Sporothrix schenckii sensu stricto, Sporothrix globosa, Sporothrix mexicana or Sporothrix albicans. The activity of catalase and glutathione were accessed in the liver and spleen. RESULTS: Animals infected with S. brasiliensis exhibited splenomegaly and significant decrease in catalase activity, and protein and non-protein thiol content compared to animals infected with the other species. CONCLUSIONS: Sporothrix brasiliensis exhibits higher pathogenicity compared to other species of the Sporothrix schenckii complex by increasing oxidative stress in animal tissue.

Gallic acid decreases vacuous chewing movements induced by reserpine in rats.

Involuntary oral movements are present in several diseases and pharmacological conditions; however, their etiology and efficient treatments remain unclear. Gallic acid is a natural polyphenolic acid found in gall nuts, sumac, oak bark, tea leaves, grapes and wine, with potent antioxidant and antiapoptotic activity. Thus, the present study investigated the effects of gallic acid on vacuous chewing movements (VCMs) in an animal model induced by reserpine. Rats received either vehicle or reserpine (1mg/kg/day, s.c.) during three days, followed by treatment with water or different doses of gallic acid (4.5, 13.5 or 40.5mg/kg/day, p.o.) for three more days. As result, reserpine increased the number of VCMs in rats, and this effect was maintained for at least three days after its withdrawal. Gallic acid at two different doses (13.5 and 40.5mg/kg/day) has reduced VCMs in rats previously treated with reserpine. Furthermore, we investigated oxidative stress parameters (DCFH-DA oxidation, TBARS and thiol levels) and Na(+),K(+)-ATPase activity in striatum and cerebral cortex, however, no changes were observed. These findings show that gallic acid may have promissory use in the treatment of involuntary oral movements.