RESUMEN
PURPOSE: To evaluate the toxicity of chronic consumption of processed foods that are rich in trans fat on the lipid composition of brain membranes, as well as its functional repercussions. METHODS: A second generation of male rats born from mothers and grandmothers supplemented with soybean oil (SOC, an isocaloric control group) or hydrogenated vegetable fat (HVF, rich in TFA) (3g/kg; p.o.) were kept under oral treatment until 90 days of age, when they were exposed to an AMPH-induced model of mania. RESULTS: The HVF group presented 0.38% of TFA incorporation in the striatum, affecting Na(+)/K(+) ATPase activity, which was decreased per se and following AMPH-exposure. The HVF group also showed increased protein carbonyl (PC) and brain-derived neurotrophic factor (BDNF) mRNA levels after AMPH administration, while these oxidative and molecular changes were not observed in the other experimental groups. Additionally, a negative correlation between striatal Na(+)/K(+) ATPase activity and PC levels (r(2)=0.49) was observed. CONCLUSION: The prolonged consumption of trans fat allows TFA incorporation and increases striatal oxidative status, thus impairing the functionality of Na(+)/K(+)-ATPase and affecting molecular targets as BDNF mRNA. We hypothesized that the chronic intake of processed foods (rich in TFA) facilitates the development of neuropsychiatric diseases, particularly bipolar disorder.
Asunto(s)
Trastorno Bipolar/metabolismo , Encéfalo/metabolismo , ARN Mensajero/biosíntesis , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Ácidos Grasos trans/toxicidad , Anfetamina/farmacología , Animales , Trastorno Bipolar/inducido químicamente , Trastorno Bipolar/enzimología , Trastorno Bipolar/genética , Encéfalo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Factor Neurotrófico Derivado del Encéfalo/genética , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Expresión Génica , Masculino , Membranas/metabolismo , Actividad Motora/efectos de los fármacos , Carbonilación Proteica , ARN Mensajero/genética , Ratas , Aceite de Soja/administración & dosificación , Ácidos Grasos trans/administración & dosificación , Ácidos Grasos trans/metabolismoRESUMEN
This study aimed to investigate the pharmacokinetics, tissue distribution and antipsychotic activity of olanzapine administered as free drug (OLA-FREE) or loaded into lipid-core nanocapsules (OLA-LNC). OLA-LNC were successfully developed with a particle size of 142 ± 4 nm and a zeta potential of -19.6 ± 0.6 mV. Pharmacokinetics and tissue distribution studies were carried out after the administration of free and nanoencapsulated olanzapine (10 mg/kg) by intraperitoneal route to male Wistar rats. Higher olanzapine concentrations and AUC(0-12 h) were found in plasma and tissues evaluated after the administration of OLA-LNC compared to the drug in the free form, resulting in a relative bioavailability of 226.7% in the plasma. As a result olanzapine loaded lipid-core nanocapsules presented pronounced and long-lasting effects on central nervous system. These nanocapsules (10 mg/kg, i.p.) significantly diminished the stereotyped behavior induced by D,L-amphetamine up to 12 hours whereas olanzapine free-form (10 mg/kg, i.p.) was effective during 03 hours only. Moreover, olanzapine loaded lipid-core nanocapsules (1.0 mg/kg, i.p.) have shown a marked sedative effect and also prevented the prepulse inhibition disruption induced by apomorphine at lower dose than olanzapine in free-form (2.5 mg/kg, i.p.). Herewith, we point to the nanoencapsulation as a strategy for reducing the concentration of olanzapine in pharmaceutical formulations.
Asunto(s)
Benzodiazepinas/administración & dosificación , Benzodiazepinas/farmacocinética , Encéfalo/metabolismo , Nanocápsulas/química , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Animales , Antipsicóticos/administración & dosificación , Antipsicóticos/química , Antipsicóticos/farmacocinética , Benzodiazepinas/química , Disponibilidad Biológica , Encéfalo/efectos de los fármacos , Difusión , Tasa de Depuración Metabólica , Nanocápsulas/administración & dosificación , Nanocápsulas/ultraestructura , Olanzapina , Especificidad de Órganos , Tamaño de la Partícula , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
Reserpine administration results in a predictable animal model of orofacial dyskinesia (OD) that has been largely used to access movement disturbances related to extrapyramidal oxidative damage. Here, OD was acutely induced by reserpine (two doses of 0.7 mg/kg subcutaneous (s.c.)), every other day for 3 days), which was administered after (experiment 1) and before (experiment 2) magnesium (Mg) supplementation (40 mg/kg/mL, peroral (p.o.)). In experiment 1, Mg was administered for 28 days before reserpine treatment, while in experiment 2, it was initiated 24 h after the last reserpine administration and was maintained for 10 consecutive days. Experiment 1 (prevention) showed that Mg supplementation was able to prevent reserpine-induced OD and catalepsy development. Mg was also able to prevent reactive species (RS) generation, thus preventing increase of protein carbonyl (PC) levels in both cortex and substantia nigra, but not in striatum. Experiment 2 (reversion) showed that Mg was able to decrease OD and catalepsy at all times assessed. In addition, Mg was able to decrease RS generation, with lower levels of PC in both cortex and striatum, but not in substantia nigra. These outcomes indicate that Mg is an important metal that should be present in the diet, since its intake is able to prevent and minimize the development of movement disorders closely related to oxidative damage in the extrapyramidal brain areas, such as OD.
Asunto(s)
Encéfalo/metabolismo , Magnesio/farmacología , Magnesio/uso terapéutico , Trastornos del Movimiento/tratamiento farmacológico , Animales , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Trastornos del Movimiento/etiología , Ratas , Ratas Wistar , Reserpina/toxicidadRESUMEN
Recently, we have described the influence of dietary fatty acids (FA) on mania-like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)-induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short- (1 h) and long- (24 h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF- mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA ratio. Interestingly, our data showed a positive correlation between brain-derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2) = 0.53; P = 0.000/r(2) = 0.32; P = 0.011, respectively), as well as a negative correlation between PC and DAT levels (r(2) = 0.23; P = 0.015). Our findings confirm that provision of n-3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania-like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions.
Asunto(s)
Trastorno Bipolar/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Efectos Tardíos de la Exposición Prenatal , ARN Mensajero/metabolismo , Ácidos Grasos trans/toxicidad , Animales , Trastorno Bipolar/psicología , Modelos Animales de Enfermedad , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Femenino , Aceites de Pescado/toxicidad , Lactancia , Masculino , Trastornos de la Memoria/metabolismo , Embarazo , Ratas Wistar , Reconocimiento en Psicología/fisiología , Aceite de Soja/toxicidad , Productos Vegetales/toxicidadRESUMEN
This study investigated the influence of neonatal handling on amphetamine-induced conditioned place preference (CPP), as well as the consequent anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Male pups were exposed to tactile stimulation (TS) or neonatal isolation (NI) for 10 min every day from postnatal day one (PND1) to PND21. After being weaned (PND22), pups were separated by handling type until PND40, when treatment with amphetamine (AMPH-4 mg/kg/mL ip, for 8 days) or vehicle (NaCl 0.9% ip, 1 mL/Kg) in CPP started. AMPH-conditioning evoked drug-preference (in 24h and 96 h) and abstinence symptoms in unhandled (UH) animals, followed by oxidative damage in the cortex, hippocampus and striatum. TS showed beneficial influence, as observed by the decreased drug-preference (24 and 96 h) in relation to UH and NI, showing no abstinence symptoms in this last period, as observed by the reduced anxiety-like symptoms. The oxidative status indicated a protective influence of TS on brain tissues: lower lipid peroxidation (LP) and reduced protein carbonylation (PC) in the cortex, hippocampus and striatum. Furthermore, TS also increased antioxidant defenses in brain tissues and blood: i) increased plasma levels of vitamin C; ii) increased activity of catalase (CAT) and iii) higher levels of glutathione (GSH) in red blood cells (RBC). Moreover, there were positive correlations of AMPH-CPP with PC and LP levels in all the brain areas assessed. In summary, TS modifies AMPH-preference in the CPP paradigm, reducing drug abstinence behaviors, and stimulating the antioxidant defense system, thus protecting the brain areas closely related to addiction in young rats. Studies about TS and addiction in animal models should be extended to the molecular level.
Asunto(s)
Anfetaminas/administración & dosificación , Conducta Adictiva , Estrés Oxidativo , Estimulación Física , Tacto , Animales , Animales Recién Nacidos , Condicionamiento Clásico , Femenino , Masculino , Aprendizaje por Laberinto , Embarazo , Ratas , Ratas WistarRESUMEN
Olanzapine is an atypical antipsychotic drug, whose chronic use has been associated with the development of potential adverse effects such as weight gain and cardio-metabolic disorders like hypercholesterolemia and diabetes. To circumvent these side effects, the controlled release of olanzapine is a promising approach to improve adhesion of schizophrenic patients to the treatment. An innovative strategy to prolong drug release consists of loading the drug into biodegradable polymeric lipid-core nanocapsules. In this study, particle size, polydispersity, pH, zeta potential and drug loading of olanzapine-loaded lipid-core nanocapsules were analyzed. Weight gain, biochemical parameters and antipsychotic activity were evaluated in male Wistar rats. The lipid-core nanocapsules had a mean diameter of 156 +/- 13 nm, a polydispersity index lower than 0.1, a pH value of 6.12 +/- 0.14, zeta potential of -17 +/- 2.40 mV and encapsulation efficiency close to 100%. The animals treated with olanzapine-loaded lipid-core nanocapsules showed significantly lower weight gain (63.4 +/- 19.6 g) and total cholesterol levels (66.2 +/- 3.5 g x dl(-1)), compared to those administered with free olanzapine (112.6 +/- 10.3 g and 90.4 +/- 2.4 g x dl(-1)), respectively. Additionally, a more prolonged antipsychotic action was observed in the stereotyped behavior animal model induced by D,L-amphetamine, which affords to conclude that nanoencapsulation is a promising alternative to treat schizophrenic patients.
Asunto(s)
Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Trastornos Mentales/inducido químicamente , Trastornos Mentales/prevención & control , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Trastornos Psicóticos/tratamiento farmacológico , Animales , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Antipsicóticos/química , Benzodiazepinas/química , Difusión , Sinergismo Farmacológico , Masculino , Nanocápsulas/efectos adversos , Nanocápsulas/ultraestructura , Olanzapina , Tamaño de la Partícula , Trastornos Psicóticos/diagnóstico , Ratas , Ratas Wistar , Propiedades de Superficie , Resultado del TratamientoRESUMEN
We investigated the influence of neonatal handling on cocaine-induced conditioned place preference (CPP), anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Pups were submitted to tactile stimulation (TS) or neonatal isolation (NI10 or NI60) after birth, and then were submitted to CPP performed with cocaine. TS group did not show place preference, while unhandled (UH), NI10 and NI60 rats did. Handling was related to anxiety-like symptoms per se in UH and NI60 groups and this behavior was also observed in the cocaine-conditioned rats exposed to the same handlings. Both TS and NI10 pups treated or not with cocaine showed less anxiety-like behavior than animals submitted to other handlings. TS reduced protein carbonyl (PC) in cortex and NI60 increased PC in both striatum and hippocampus of cocaine-treated rats. Among cocaine-treated rats, both times of NI increased plasma lipoperoxidation levels, which was reduced by TS in erythrocytes. TS increased the catalase activity in brain areas, while other handlings did not change this. Both TS and NI10 increased plasma vitamin C levels. These findings indicate that neonatal handling can modify anxiety-like symptoms related to cocaine preference and abstinence, and its protective influence, especially TS, on the antioxidant system.
Asunto(s)
Animales Recién Nacidos/fisiología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Trastornos Relacionados con Cocaína/psicología , Estrés Oxidativo/fisiología , Estimulación Física , Aislamiento Social/psicología , Animales , Antioxidantes/metabolismo , Ansiedad/psicología , Ácido Ascórbico/sangre , Ácido Ascórbico/metabolismo , Química Encefálica/fisiología , Catalasa/metabolismo , Condicionamiento Operante/fisiología , Eritrocitos/metabolismo , Femenino , Manejo Psicológico , Embarazo , Carbonilación Proteica/fisiología , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
The current Western diet often provides considerable amounts of saturated and trans fatty acids (TFA), whose incorporation into neuronal membranes has been implicated in changes of brain neurochemical functions. Such influence has caused concerns due to precipitation of neuropsychiatric disorders, whose data are still unclear. Here we evaluated the influence of different fats on preference parameters for amphetamine (AMPH): adolescent rats were orally supplemented with soybean oil (SO, rich in n-6 FA, which was considered an isocaloric control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in saturated and trans FA) from weaning, which were born of dams supplemented with the same fat from pregnancy and lactation. AMPH preference, anxiety-like symptoms and locomotor index were evaluated in conditioned place preference (CPP), elevated plus maze (EPM) and open-field (OF), respectively, while brain oxidative status was determined in cortex, striatum and hippocampus. HVF increased AMPH-CPP and was associated with withdrawal signs, as observed by increased anxiety-like symptoms. Moreover, SO and FO were not associated with AMPH preference, but only FO-supplemented rats did not show any anxiety-like symptoms or increased locomotion. FO supplementation was related to lower oxidative damages to proteins and increased CAT activity in striatum and hippocampus, as well as increased GSH levels in blood, while HVF was related to increased oxidative status. In conclusion, our study showed the harmful influence of TFA on AMPH-CPP and drug craving symptoms, which can be related to dopaminergic neurotransmission.
Asunto(s)
Anfetamina/farmacología , Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos trans/farmacología , Animales , Condicionamiento Clásico , Femenino , Ratas , Ratas WistarRESUMEN
This study investigated the protective effect of pecan nut (Carya illinoensis) shell aqueous extract (AE) on the oxidative and morphological status of rat testis treated with cyclophosphamide (CP). Wistar rats received water or AE (5%) ad libitum for 37 days. On day 30, half of each group received a single intraperitoneal administration of vehicle or CP 200 mg/kg. After 7 days, the animals were killed and their testis removed. Rats treated with CP presented reduced levels of lactate dehydrogenase, vitamin C, and gluthatione, as well as decreased catalase activity, increased lipid peroxidation levels and superoxide dismutase activity, no alteration in carbonyl protein levels, and a loss of morphological testicular integrity. In contrast, cotreatment with pecan shell AE totally prevented the decrease of lactate dehydrogenase and vitamin C levels and catalase activity and partially prevented the depletion of gluthatione levels. Moreover, it totally prevented the increase in superoxide dismutase activity and lipid peroxidation levels and maintained testicular integrity. These findings show the protective role of pecan shell AE in CP-induced testicular toxicity. The use of this phytotherapy may be considered to minimize deleterious effects related to this chemotherapy.
Asunto(s)
Carya , Ciclofosfamida/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Testículo/metabolismo , Testículo/patología , Animales , Ácido Ascórbico/metabolismo , Catalasa/metabolismo , Ciclofosfamida/efectos adversos , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Modelos Animales , Nueces , Fitoterapia , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Testículo/efectos de los fármacosRESUMEN
This study investigated the influence of neonatal handling on behavioral and biochemical consequences of chronic mild stress (CMS) in adulthood. Male rat pups were submitted to daily tactile stimulation (TS) or maternal separation (MS), from postnatal day 1 (PND1) to postnatal day 21 (PND21), for 10 min/day. In adulthood, half the number of animals were exposed to CMS for 3 weeks and submitted to behavioral testing, including sucrose preference (SP), elevated plus maze (EPM), and defensive burying tasks (DBTs), followed by biochemical assessments. CMS reduced SP, increased anxiety in EPM and DBT, and increased adrenal weight. In addition, CMS decreased plasma vitamin C (VIT C) levels and increased protein carbonyl (PC) levels, catalase (CAT) activity in hippocampus and cortex, and superoxide dismutase (SOD) levels in cortex. In contrast, both forms of neonatal handling were able to prevent reduction in SP, anxiety behavior in DBT, and CMS-induced adrenal weight increase. Furthermore, they were also able to prevent plasma VIT C reduction, hippocampal PC levels increase, CAT activity increase in hippocampus and cortex, and SOD levels increase in cortex following CMS. Only TS was able to prevent CMS-induced anxiety symptoms in EPM and PC levels in cortex. Taken together, these findings show the protective role of neonatal handling, especially TS, which may enhance ability to cope with stressful situations in adulthood.
Asunto(s)
Ansiedad/prevención & control , Conducta Animal , Manejo Psicológico , Estrés Oxidativo , Estrés Psicológico/complicaciones , Adaptación Psicológica , Glándulas Suprarrenales/patología , Factores de Edad , Animales , Animales Recién Nacidos , Ansiedad/sangre , Ansiedad/etiología , Ansiedad/patología , Ansiedad/psicología , Ansiedad de Separación/psicología , Ácido Ascórbico/sangre , Biomarcadores/sangre , Catalasa/sangre , Corteza Cerebral/metabolismo , Condicionamiento Psicológico , Preferencias Alimentarias , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto , Tamaño de los Órganos , Carbonilación Proteica , Ratas , Ratas Wistar , Estrés Psicológico/sangre , Estrés Psicológico/patología , Estrés Psicológico/psicología , Sacarosa , Superóxido Dismutasa/sangre , TactoRESUMEN
In this study we evaluated the influence of neonatal tactile stimulation (TS) on behavioral and biochemical effects related to a low dose of diazepam (DZP) in adult rats. Male pups of Wistar rats were handled (TS) daily from PND1 to PND21 for 10 min, while unhandled (UH) rats were not touched. In adulthood, half the animals of each group received a single administration of diazepam (0.25mg/kg body weight i.p.) or vehicle and then were submitted to behavioral and biochemical evaluations. In the TS group, DZP administration reduced anxiety-like symptoms in different behavioral paradigms (elevated plus maze, EPM; staircase and open-field and defensive burying) and increased exploratory behavior. These findings show that neonatal TS increased DZP pharmacological responses in adulthood compared to neonatally UH animals, as observed by reduced anxiety-like symptoms and lower levels of plasma cortisol. TS also changed plasma levels of antioxidant defenses such as vitamin C and glutathione peroxidase, whose increase may be involved in lower oxidative damages to proteins in cortex, subthalamic region and hippocampus of these animals. Here we are showing for the first time that neonatal TS is able to change responsiveness to benzodiazepine drugs in adulthood and provides better pharmacological responses in novel situations of stress.
Asunto(s)
Ansiolíticos/farmacología , Ansiedad/fisiopatología , Diazepam/farmacología , Estimulación Física/métodos , Tacto/fisiología , Animales , Animales Recién Nacidos , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Masculino , Ratas , Ratas Wistar , Estrés Psicológico/tratamiento farmacológicoRESUMEN
Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal.
Asunto(s)
Enfermedades de los Ganglios Basales/tratamiento farmacológico , Enfermedades de los Ganglios Basales/prevención & control , Carya/química , Modelos Animales de Enfermedad , Nueces/química , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Catalepsia/inducido químicamente , Catalepsia/tratamiento farmacológico , Haloperidol , Masculino , Trastornos del Movimiento/tratamiento farmacológico , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , ReserpinaRESUMEN
In the last decades, foods rich in omega-3 (ω-3) fatty acids (FA) have been replaced by omega-6 (ω-6) and trans FA, which are found in processed foods. The influence of ω-6 (soybean oil--SO), trans (hydrogenated vegetable fat--HVF) and ω-3 (fish oil--FO) fatty acids on locomotor and oxidative stress (OS) parameters were studied in an animal model of mania. Rats orally fed with SO, HVF and FO for 8 weeks received daily injections of amphetamine (AMPH--4 mg/kg/mL-ip) for the last week of oral supplementation. HVF induced hyperactivity, increased the protein carbonyl levels in the cortex and decreased the mitochondrial viability in cortex and striatum. AMPH-treatment increased the locomotion and decreased the mitochondrial viability in all groups, but its neurotoxicity was higher in the HVF group. Similarly, AMPH administration increased the protein carbonyl levels in striatum and cortex of HVF-supplemented rats. AMPH reduced the vitamin-C plasmatic levels of SO and HVF-fed rats, whereas no change was observed in the FO group. Our findings suggest that trans fatty acids increased the oxidative damage per se and exacerbated the AMPH-induced effects. The impact of trans fatty acids consumption on neuronal diseases and its consequences in brain functions must be further evaluated.
Asunto(s)
Anfetaminas/farmacología , Trastorno Bipolar/inducido químicamente , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Anfetaminas/administración & dosificación , Anfetaminas/efectos adversos , Animales , Ácido Ascórbico/sangre , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Sinergismo Farmacológico , Ácidos Grasos Omega-3/efectos adversos , Ácidos Grasos Omega-6/efectos adversos , Locomoción/efectos de los fármacos , RatasRESUMEN
Haloperidol is an antipsychotic drug associated with the development of movement disorders. We evaluated the effect of its nanoencapsulation on its pharmacological activity and motor side effects. Haloperidol-loaded polysorbate-coated nanocapsules (H-NC) showed nanometric size, negative zeta potential and low polydispersity indices and high encapsulation efficiency (>95%). Rats received a single dose of H-NC (0.2mg/kg ip) and four doses of D,L-amphetamine, AMPH (8.0mg/kg ip), injected every 3h (0, 3, 6 and 9h). The AMPH-induced stereotyped movements were quantified in the intervals of 15 min after each of four doses of AMPH, demonstrating greater pharmacological efficacy of the H-NC over free haloperidol (FH). The acute motor side effects were evaluated 1h after a single dose of H-NC or its free solution (0.2mg/kg ip). The group treated with H-NC presented lower extrapyramidal effects (catalepsy and oral dyskinesia) than those treated with FH. In the last experimental set, rats sub-chronically treated with a daily dose of H-NC (0.2mg/kg ip) for 28 days showed a lower incidence of extrapyramidal effects than those treated with the free drug (0.2mg/kg ip). Our findings showed the potential of using H-NC in the development of a nanomedicine aimed at increasing the efficacy of this antipsychotic drug and reducing its side effects.