RESUMEN
Ascorbic acid (AA) administration has been associated with neuroprotection against oxidative stress, although at high doses it can facilitate oxidation and acts like a proconvulsing drug. The pilocarpine-induced epilepsy model has been widely studied. However, less is known about the effects of sub-convulsive doses of pilocarpine on brain activity in immature animals under normal or deficient nutritional conditions. Herein, we investigated the effects of chronic pilocarpine administration in a sub-convulsive dose, with or without AA, on the excitability-related phenomenon denominated as cortical spreading depression (CSD) and levels of lipid peroxidation-induced malondialdehyde in well-nourished and malnourished rats. At postnatal days 7-28, rats received no gavage treatment (naïve group), saline (vehicle group), 45 mg/kg/d of pilocarpine and/or 120 mg/kg/d of AA. CSD propagation and malondialdehyde levels were analyzed at 34-40 days. The pilocarpine group presented with lower CSD velocities, while AA groups exhibited higher CSD velocities and augmented malondialdehyde levels compared with controls. The co-administration of AA partially antagonized the pilocarpine CSD effects, but did not revert it to control levels. Malnutrition increased CSD amplitude and velocity in comparison to the well-nourished condition. The electrocorticogram (ECoG) amplitude increased after CSD (ECoG potentiation) when compared with the baseline amplitude before CSD. However, no intergroup difference was observed in this CSD-related ECoG potentiation. The results support the hypothesis of a pilocarpine/ascorbic acid interaction in the immature rat brain and might help further the understanding of this interaction on neuronal electrical activity and oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Agonistas Muscarínicos/farmacología , Pilocarpina/farmacología , Animales , Encéfalo/fisiología , Encéfalo/fisiopatología , Depresión de Propagación Cortical/efectos de los fármacos , Interacciones Farmacológicas , Electrocorticografía , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Desnutrición/fisiopatología , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas WistarRESUMEN
OBJECTIVES: Goat whey, a usually discarded byproduct from goat cheese manufacturing, is a good source of sialic acid (SA), an oligosaccharide that is involved in processes such as memory and brain excitability. Here, we investigated in rats the effect of dried goat whey (DGW) on memory and the brain excitability-dependent phenomenon known as cortical spreading depression (CSD). We also provide evidence for the involvement of SA in this effect. In addition, we tested animals under unfavorable suckling conditions to evaluate whether nutritional deficiency would modulate DGW action. METHODS: Wistar rats were suckled in litters with 9 and 15 pups (groups L9 and L15, respectively). From postnatal (P) days 7-14, the animals received per gavage 17.45â g of DGW/kg/day, or SA (20â mg/kg/day or 100â mg/kg/day). At P28-30, we tested the animals' memory in the object recognition paradigm. At P35-45 we recorded CSD and analyze its velocity of propagation, amplitude, and duration. RESULTS: In the object recognition test, the L15 DGW-treated rats performed better than the L15-controls. The L15 rats displayed higher CSD velocities compared with L9 groups. The DGW and SA groups exhibited higher CSD velocity than the naïve- and saline-treated controls, regardless the lactation status (P < 0.05). DISCUSSION: Our results documented a novel effect of DGW on memory and CSD. SA dose-dependently facilitated CSD, suggesting its involvement on the DGW action. DGW is considered a potential supplement to improve brain development and function in malnourished children, and this shall be further translationally investigated.
Asunto(s)
Depresión de Propagación Cortical/efectos de los fármacos , Tamaño de la Camada , Memoria/efectos de los fármacos , Ácido N-Acetilneuramínico/farmacología , Suero Lácteo/administración & dosificación , Animales , Animales Recién Nacidos , Queso , Femenino , Cabras , Masculino , Ratas , Ratas Wistar , Suero Lácteo/químicaRESUMEN
Chronic ethanol ingestion, mostly in young adults, constitutes a frequent drug-abuse situation, which is associated to a wide variety of pathological disturbance affecting a number of organs, including liver, kidney, heart, pancreas and brain. The ethanol effects are more prominent when occurring at the perinatal period of life, generating, among other disabilities, brain developmental and functional impairments, as well as the so-called "fetal alcoholic syndrome". However, low doses of ethanol, although not producing conspicuous signs of physiological impairment, may affect the developing organism, impairing the renal and cardiovascular system, among others. As a consequence of increased oxidative stress produced by ethanol intake and its subsequent oxidation, lipid peroxidation increases, enhancing reactive oxygen species formation, which is potentially injurious to the brain tissue. When occurring during gestation, lipid peroxidation may occur in the placenta, an event that would partially be responsible for fetal nutrition disturbance and consequently late physiological impairment. In this short review, data on ethanol effects on the nervous and cardiorenal structure and function are analyzed at the light of the most relevant hypotheses concerning ethanol mechanisms of action. Additionally, experimental data from the authors' laboratories are presented and discussed, focusing particular attention to the possibility of differential neural and cardiorenal ethanol effects as a function of the dose used in distinct experimental models.
Asunto(s)
Alcoholismo/complicaciones , Etanol/efectos adversos , Trastornos del Espectro Alcohólico Fetal/etiología , Estrés Oxidativo/efectos de los fármacos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/genética , Alcohólicos/psicología , Animales , Encéfalo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Feto/efectos de los fármacos , Homeostasis/efectos de los fármacos , Riñón/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Se evaluó, en ratas albino, la potencialidad nutricional de una dieta (Dieta Básica Regional - DBR) constituida, en términos de claidad y cantidad por cuatro alimentos que, encuestas dietéticas, revelaron ser preferenciales en el Nordeste del Brasil. Se comparó a una dieta balanceada, con 22% de caseína. En la DBR se determinó la relación GCal% estimándose las vitaminas a partir de datos en la literatura. Se comprobó qye la DBR era muy pobre, no era una dieta balanceada; además era deficiente en ciertos nutrientes, sobre todo en proteínas (7.8%). La curva ponderal de los animales que recibían la dieta fue severamente afectada; la diferencia entre dicha curva y la de los controles se acentuó con la edad, sin que se detectaran diferencias entre sexos, en los fetos y las ratas lactantes, el peso del hígado y el del diafragma eran muy bajos y paralelos al peso corporal y del encéfalo, que pesó un poco menos que el de los controles, pero con peso relativo (20%) mayor. Las hembras con DBR preñadas, acusaron menos aumento de peso, aunque su ingestión fue mayor que la de las controles. Durante la lactancia, tanto el aumento de peso como la ingestión fueron menores que en las ratas control. La defunción entre los lactantes fue muy elevada. Los resultados configuran un cuadro de desnutrición al tipo de desnutrición prevalente en la Región. Se considera así que con la DBR se dispone de un modelo dietético adeucado para profundizar el estudo experimental de la desnutrición. Su diseño experimental puede ser aplciado en países cuyos alimentos básicos sean comunes a los de la DBR, predominantemente vegetal, y de condiciones socioeconómicas de consumo similares a las de regiones donde dicha dieta es la habitual