Vitaminas B1, B6, B12 e complexo B na prevenção da discinesia orofacial induzida porhaloperidol em ratos: avaliação comportamental e mecanismos associados

A Discinesia tardia (DT) é caracterizada por movimentos involuntários, principalmente na parte inferior da face, próximos da boca, com espasmos que podem ser leves ou severos. É uma alteração motora grave relacionada, mas não restrita à terapia antipsicótica. Tratamentos com antipsicóticos principalmente os da classe dos típicos, como o haloperidol (HAL) aumentam os riscos de DT. A fisiopatologia da DT é associada a um desequilíbrio em sistemas de neurotransmissão, dentre eles dopaminérgico e colinérgico, bem como com desequilíbrio oxidativo, principalmente em áreas cerebrais relacionadas ao controle do movimento, como o corpo estriado. As vitaminas (vit.) B, por sua vez, apresentam efeitos antioxidantes sendo cofatores para enzimas relacionadas à síntese de neurotransmissores. Neste contexto, o presente trabalho teve como objetivo determinar os efeitos preventivos das vit. B1, B6, B12 ou Complexo B na discinesia orofacial (DO) induzida por HAL em ratos. Foram utilizados ratos Wistar machos tratados por via intraperitoneal com HAL (1 mg/kg, i.p.) por 21 dias ou concomitantemente com HAL e as vit. B1 (60 mg/kg), B6 (60 mg/kg) ou B12 (0,6 mg/kg) por via subcutânea, sozinhas ou em associação (complexo B). O complexo B consistiu na mistura das 3 vitaminas em iguais proporções. Um grupo de animais foi administrado clozapina (25 mg/kg), um antipsicótico atípico não relacionado ao desenvolvimento de DO. Os testes comportamentais foram realizados após 30 minutos no 1º, 7º e 21º dias de administração das fármacos e consistiram na determinação da atividade locomotora, catalepsia e movimentos de mastigação no vazio...

Tardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21stday the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21stday...

(-)-α-Bisabolol-induced gastroprotection is associated with reduction in lipid peroxidation, superoxide dismutase activity and neutrophil migration.

This work examined the gastroprotection of (-)-α-bisabolol, an unsaturated optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants. (-)-α-Bisabolol has been described as a compound capable of reducing the gastric ulcer area in response to absolute ethanol. We evaluated the gastroprotection of (-)-α-bisabolol in ethanol-induced gastric lesions model through histopathological assessment, measurement of the membrane lipids peroxidation (MDA), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity and the nitrite amount. Our results showed that (-)-α-bisabolol was able to reduce injuries associated with the administration of ethanol and the formation of thiobarbituric acid reactive substances (MDA) was also able to increase SOD activity and reduce the influx of cells inflammatory (neutrophils) in the gastric mucosa. The effect of (-)-α-bisabolol seems to be unrelated to the nitric oxide. (-)-α-Bisabolol caused a reduction of catalase activity. These findings show that (-)-α-bisabolol is able to decrease oxidative stress and inflammatory event associated with the lesions induced by ethanol.

B vitamins attenuate haloperidol-induced orofacial dyskinesia in rats: possible involvement of antioxidant mechanisms.

Tardive dyskinesia (TD) is a serious motor disorder related to antipsychotic therapy, whose pathophysiology is associated to oxidative stress. Treatments that maintain antipsychotic efficacy while reducing TD risk are awaited. Haloperidol (HAL), a typical antipsychotic, is used as a putative murine model of TD. Here, we evaluated the protective role of vitamins B1, B6, and B12 alone or in combination (vitamin B cocktail) in preventing the HAL-induced orofacial dyskinesia (OD), based on their antioxidant properties. HAL (1 mg/kg) administered intraperitoneally to Wistar rats for 21 days caused OD and increased catalepsy time. The daily administration of B vitamins (B1 : B6 : B12 at 60 : 60 : 0.6 mg/kg) alone or the vitamin B cocktail, along with HAL, prevented the development of OD. Catalepsy time reduced in all groups treated with B vitamins, but to a lesser extent than OD. The participation of oxidative stress was assessed by the determination of reduced glutathione (GSH) levels and lipid peroxide formation in the striatum. HAL significantly decreased GSH levels and enhanced lipid peroxidation, whereas B1, B12, and vitamin B cocktail prevented the decrease in GSH levels. All groups treated with B vitamins presented a decrease in lipid peroxide formation. The data suggest a promising role for B vitamins in the prevention of OD.