RESUMEN
A Ketogenic Diet (KD) mimics the anticonvulsant effects of fasting, which are known to suppress seizures. The purinergic system has been investigated in the matter of epilepsy development, especially the nucleoside adenosine, which has been considered a natural brain anticonvulsant. During epileptic seizures, extracellular adenosine concentration rises rapidly to micromolar levels. Adenosine can exert its anticonvulsant functions, after its release by nucleoside bidirectional transport, or by production through the sequential catabolism of ATP by ectonucleotidases, such as E-NTPDases (ectonucleoside triphosphate diphosphohydrolases) and ecto-5'-nucleotidase. Here, we have investigated the effect of a ketogenic diet on the nucleotide hydrolysis and NTPDases expression in the lithium-pilocarpine (Li-Pilo) model of epilepsy. For the induction of Status Epileticus (SE), 21-day-old female Wistar rats received an i.p. injection of lithium chloride (127 mg/kg) and 18-19 h later an i.p. injection of pilocarpine hydrochloride (60 mg/kg). The control groups received an injection of saline. After induction of SE, the control and Li-Pilo groups received standard or ketogenic diets for 6 weeks. The lithium-pilocarpine exposure affected the ATP (a decrease of between 8 % and 16 %) and ADP (an increase of between 18 % and 22 %) hydrolysis in both groups whereas the diet did not impact the nucleotide hydrolysis. NTPDase2 and 3 mRNA expressions decreased in the Li-Pilo group (41 % and 42 %). This data highlights the participation of the purinergic system in the pathophysiology of this model of epilepsy, since nucleotide hydrolysis and NTPDase expressions were altered by Li-Pilo exposure, with no significant effects of the ketogenic diet. However, the interaction between purinergic signaling and a ketogenic diet on epilepsy still needs to be better elucidated.
Asunto(s)
5'-Nucleotidasa/metabolismo , Antimaníacos , Dieta Cetogénica , Cloruro de Litio , Agonistas Muscarínicos , Pilocarpina , Estado Epiléptico/inducido químicamente , Estado Epiléptico/enzimología , 5'-Nucleotidasa/efectos de los fármacos , Adenosina Difosfato/metabolismo , Adenosina Monofosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Femenino , Hidrólisis , Cetonas/sangre , Nucleótidos/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/metabolismoRESUMEN
Neonatal hypoxic-ischemic encephalopathy (HI) is a major cause of nervous system damage and neurological morbidity. Perinatal malnutrition affects morphological, biochemical and behavioral aspects of neural development, including pathophysiological cascades of cell death triggered by ischemic events, so modifying resulting brain damage. Female Wistar rats were subjected to protein restriction during pregnancy and lactation (control group: 25% soybean protein; malnourished group: 7%). Seven days after delivery (PND7), their offspring were submitted to unilateral cerebral HI; rats were then tested for sensorimotor (PND7 and PND60) and memory (PND60) functions. Offspring of malnourished mothers showed marked reduction in body weight starting in lactation and persisting during the entire period of observation. There was a greater sensorimotor deficit after HI in malnourished (M) animals, in righting reflex and in home bedding task, indicating an interaction between diet and hypoxia-ischemia. At PND60, HI rats showed impaired performance when compared to controls in training and test sessions of rota-rod task, however there was no effect of malnutrition per se. In the open field, nourished HI (HI-N) presented an increase in crossings number; this effect was not present in HI-M group. Surprisingly, HI-M rats presented a better performance in inhibitory avoidance task and a smaller hemispheric brain damage as compared to HI-N animals. Our data points to a possible metabolic adaptation in hypoxic-ischemic animals receiving protein malnutrition during pregnancy and lactation; apparently we observed a neuroprotective effect of diet, possibly decreasing the brain energy demand, under a hypoxic-ischemic situation.
Asunto(s)
Trastornos Nutricionales en el Feto/fisiopatología , Hipoxia-Isquemia Encefálica/fisiopatología , Desnutrición Proteico-Calórica/fisiopatología , Animales , Reacción de Prevención , Peso Corporal , Dieta con Restricción de Proteínas , Proteínas en la Dieta/administración & dosificación , Femenino , Hipoxia-Isquemia Encefálica/patología , Lactancia , Memoria , Actividad Motora , Embarazo , Complicaciones del Embarazo/fisiopatología , Ratas , Ratas Wistar , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
OBJECTIVE: We measured the in vitro effects of mercuric chloride (Hg2+) and selenite (Se4+) on hepatic 2-thiobarbituric acid-reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol. METHODS: Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 microM) and sodium selenite (25 microM) for 1 h. RESULTS: The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil (P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se4+ and Hg2+ chloride that after exposure to Se4+ alone, suggesting an interaction between Hg2+ and Se4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity. CONCLUSION: Together these results indicated that the protective effect of Se4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.