Alcindo Busanello

Resveratrol protects against a model of vacuous chewing movements induced by reserpine in mice.

Reserpine treatment is a putative animal model of orofacial dyskinesia, tremor, and Parkinsonism. Here, we examined the effects of resveratrol, a polyphenol with neuroprotective properties primarily contained in red grapes and red wine, in an animal model of vacuous chewing movements (VCMs) induced by treatment with reserpine. Mice were treated with reserpine (1 mg/kg, subcutaneously on days 1 and 3) and/or resveratrol (5 mg/kg, intraperitoneally 3 consecutive days). VCM, locomotor, and exploratory performance were evaluated. Reserpine treatment produced an increase in VCM intensity, which was significantly reduced by resveratrol co-treatment. Reserpine also decreased locomotor and exploratory activity in the open field test. However, resveratrol co-treatment was not able to protect against these effects. The data suggest that resveratrol could be a promising pharmacological tool for studying VCM in rodents. However, further investigations are needed to understand the exact mechanisms involved in the neuroprotective effects of resveratrol.

Effects of diphenyl diselenide on methylmercury toxicity in rats.

This study investigates the efficacy of diphenyl diselenide [(PhSe)2] in attenuating methylmercury- (MeHg-)induced toxicity in rats. Adult rats were treated with MeHg [5 mg/kg/day, intragastrically (i.g.)] and/ or (PhSe)2 [1 mg/kg/day, intraperitoneally (i.p.)] for 21 days. Body weight gain and motor deficits were evaluated prior to treatment, on treatment days 11 and 21. In addition, hepatic and cerebral mitochondrial function (reactive oxygen species (ROS) formation, total and nonprotein thiol levels, membrane potential (ΔΨm), metabolic function, and swelling), hepatic, cerebral, and muscular mercury levels, and hepatic, cerebral, and renal thioredoxin reductase (TrxR) activity were evaluated. MeHg caused hepatic and cerebral mitochondrial dysfunction and inhibited TrxR activity in liver (38,9%), brain (64,3%), and kidney (73,8%). Cotreatment with (PhSe)2 protected hepatic and cerebral mitochondrial thiols from depletion by MeHg but failed to completely reverse MeHgs effect on hepatic and cerebral mitochondrial dysfunction or hepatic, cerebral, and renal inhibition of TrxR activity. Additionally, the cotreatment with (PhSe)2 increased Hg accumulation in the liver (50,5%) and brain (49,4%) and increased the MeHg-induced motor deficits and body-weight loss. In conclusion, these results indicate that (PhSe)2 can increase Hg body burden as well as the neurotoxic effects induced by MeHg exposure in rats.

Resveratrol reduces vacuous chewing movements induced by acute treatment with fluphenazine

Treatment with classical neuroleptics in humans can produce a serious side effect, known as tardive dyskinesia (TD). Here, we examined the possible neuroprotective effects of resveratrol, a polyphenol compound contained in red grapes and red wine, in an animal model of orofacial dyskinesia (OD) induced by acute treatment with fluphenazine. Adult male rats were treated during 3 weeks with fluphenazine enantate (25 mg/kg, i.m., single administration) and/or resveratrol (1 mg/kg, s.c., 3 times a week). Vacuous chewing movements (VCMs), locomotor and exploratory performance were evaluated. Fluphenazine treatment produced VCM in 70% of rats and the concomitant treatment with resveratrol decreased the prevalence to 30%, but did not modify the intensity of VCMs. Furthermore, the fluphenazine administration reduced the locomotor and exploratory activity of animals in the open field test. Resveratrol co-treatment was able to protect the reduction of both parameters. Taken together, our data suggest that resveratrol could be considered a potential neuroprotective agent by reducing motor disorders induced by fluphenazine treatment.

Antidepressant-Like Effect of Ilex paraguariensis in Rats

In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect.

Centella asiatica and Its Fractions Reduces Lipid Peroxidation Induced by Quinolinic Acid and Sodium Nitroprusside in Rat Brain Regions.

Oxidative stress has been implicated in several pathologies including neurological disorders. Centella asiatica is a popular medicinal plant which has long been used to treat neurological disturbances in Ayurvedic medicine. In the present study, we quantified of compounds by high performance liquid chromatography (HPLC) and examined the phenolic content of infusion, ethyl acetate, n-butanolic and dichloromethane fractions. Furthermore, we analyzed the ability of the extracts from C. asiatica to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) radical as well as total antioxidant activity through the reduction of molybdenum (VI) (Mo6+) to molybdenum (V) (Mo5+). Finally, we examined the antioxidant effect of extracts against oxidant agents, quinolinic acid (QA) and sodium nitroprusside (SNP), on homogenates of different brain regions (cerebral cortex, striatum and hippocampus). The HPLC analysis revealed that flavonoids, triterpene glycoside, tannins, phenolic acids were present in the extracts of C. asiatica and also the phenolic content assay demonstrated that ethyl acetate fraction is rich in these compounds. Besides, the ethyl acetate fraction presented the highest antioxidant effect by decreasing the lipid peroxidation in brain regions induced by QA. On the other hand, when the pro-oxidant agent was SNP, the potency of infusion, ethyl acetate and dichloromethane fractions was equivalent. Ethyl acetate fraction from C. asiatica also protected against thiol oxidation induced by SNP and QA. Thus, the therapeutic potential of C. asiatica in neurological diseases could be associated to its antioxidant activity.

Effect of Hypericum perforatum on different models of movement disorders in rats.

The effects of Hypericum perforatum, a plant with antidepressant action, were evaluated in models of abnormal movements in rats, brought about by administration of fluphenazine or reserpine. The number of vacuous chewing movements (VCMs) and locomotor activity (the number of crossings and rears in the open field test) were measured. In experiment 1, rats received a single administration of fluphenazine enanthate (25 mg/kg, intramuscular) and/or daily treatment with H. perforatum (300 mg/kg, in place of drinking water) for 7 days. Fluphenazine increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the locomotor activity. In experiment 2, rats received reserpine every 2 days for 6 days (0.5 mg/kg, subcutaneous) and/or H. perforatum (300 mg/kg, in place of drinking water) daily for 16 days beginning 10 days before the first administration of reserpine. Reserpine treatment increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the number of rears but did prevent the effect of reserpine on the number of crossings. In conclusion, H. perforatum failed to protect against orofacial movements induced by fluphenazine or reserpine in rats.

Anandamide attenuates haloperidol-induced vacuous chewing movements in rats

Antipsychotics may cause tardive dyskinesia in humans and orofacial dyskinesia in rodents. Although the dopaminergic system has been implicated in these movement disorders, which involve the basal ganglia, their underlying pathomechanisms remain unclear. CB1 cannabinoid receptors are highly expressed in the basal ganglia, and a potential role for endocannabinoids in the control of basal ganglia-related movement disorders has been proposed. Therefore, this study investigated whether CB1 receptors are involved in haloperidol-induced orofacial dyskinesia in rats. Adult male rats were treated for four weeks with haloperidol decanoate (38mg/kg, intramuscularly - i.m.). The effect of anandamide (6nmol, intracerebroventricularly - i.c.v.) and/or the CB1 receptor antagonist SR141716A (30μg, i.c.v.) on haloperidol-induced vacuous chewing movements (VCMs) was assessed 28days after the start of the haloperidol treatment. Anandamide reversed haloperidol-induced VCMs; SR141716A (30μg, i.c.v.) did not alter haloperidol-induced VCM per se but prevented the effect of anandamide on VCM in rats. These results suggest that CB1 receptors may prevent haloperidol-induced VCMs in rats, implicating CB1 receptor-mediated cannabinoid signaling in orofacial dyskinesia.