Lipoic acid protects C6 cells against ammonia exposure through Na⁺-K⁺-Cl⁻ co-transporter and PKC pathway.

Astrocytes play an essential role in the central nervous system (CNS) homeostasis. They providing metabolic support and protecting against oxidative stress and glutamatergic excitotoxicity. Glutamate uptake, an electrogenic function, is driven by cation gradients and the Na⁺-K⁺-Cl⁻ co-transporter (NKCC1) carries these ions into and out of the cell. Elevated concentrations of ammonia in the brain lead to cerebral dysfunction. Ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and ion discharged. Astrocytes also convert excess ammonia and glutamate into glutamine, via glutamine synthetase (GS). Lipoic acid (LA) is a modulator of the cellular redox status potentially beneficial in neurodegenerative diseases. In this study, we investigated the effect of LA on glial parameters, in C6 cells exposed to ammonia. Ammonia increased S100B secretion and decreased glutamate uptake, GS activity and glutathione (GSH) content. LA was able to prevent these effects. LA exerts its protective effect on glutamate uptake and S100B secretion via mechanisms dependent of NKCC1 and PKC. These findings show that LA is able to modulate glial function impairments by ammonia in vitro, indicating a potential therapeutic agent to improve glutamatergic metabolism and oxidative stress against hyperammonemia.

El ácido lipoico reduce la ganancia de peso inducida por dieta alta en grasa: efectos sobre el transporte intestinal de azúcares / Lipoic acid prevents body weight gain induced by a high fat diet in rats: Effects on intestinal sugar transport

Several studies have suggested that oxidative stress might cause and aggravate theinflammatory state associated with obesity and could be the link between excessiveweight gain and its related disorders such as insulin resistance and cardiovascular diseases.Thus, antioxidant treatment has been proposed as a therapy to prevent andmanage obesity and associated complications. Therefore, the aim of the present studywas to investigate the effects of supplementation of a standard or high fat diet withthe antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feedefficiency and intestinal sugar absorption, in male Wistar rats. LA supplementationinduced a lower body weight gain and adipose tissue size in both control or high fatfed rats accompanied by a reduction in food intake. The group fed on a high fat dietand treated with LA (OLIP group) showed a lower body weight gain than its correspondingPair-Fed (PF) group (P<0.05), which received the same amount of foodthan LA-treated animals but with no LA. In fact, LA induced a reduction on feedefficiency and also significantly decreased intestinal α-methylglucoside (α-MG)absorption both in lean and obese rats. These results suggest that the beneficial effectsof dietary supplementation with LA on body weight gain are mediated, at least inpart, by the reduction observed in food intake and feed efficiency. Furthemore, theinhibitory action of LA on intestinal sugar transport could explain in part the lowerfeed efficiency observed in LA-treated animals and therefore, highlighting the beneficialeffects of LA on obesity(AU)

Varios estudios han sugerido que el estresoxidativo podria actuar como desencadenantey agravante del estado inflamatorio asociado ala obesidad y podria ser un potencial nexo deunion entre la excesiva ganancia de peso y lasco-morbilidades asociadas. Asi, se ha propuestoel tratamiento con antioxidantes naturalescomo posible terapia contra el desarrollo deobesidad asi como sus complicaciones asociadas.Por ello, el objeto del presente trabajo fueinvestigar en ratas Wistar macho los efectos dela suplementacion de una dieta estandar o altaen grasa con un antioxidante, el acido lipoico(AL) (0,25g/ 100g de comida) durante 56 diassobre la ganancia de peso corporal, la adiposidad,la eficiencia metabolica y la absorcionintestinal de azucares. La suplementacion de ladieta con AL indujo una menor ganancia depeso corporal y redujo el tamano del tejidoadiposo blanco total, tanto en ratas alimentadascon dieta control como alta en grasa. Ademas,disminuyo la ingesta. La ganancia de pesoen el grupo alimentado con dieta alta en grasay AL fue menor que la de su correspondientegrupo Pair-Fed (P<0,05), el cual recibia lamisma cantidad de comida que los animalestratados con AL pero sin este acido. De hecho,la suplementacion con acido lipoico redujo laeficiencia metabolica y disminuyo significativamentela absorcion intestinal de ƒ¿-metilglucosido(ƒ¿-MG) tanto en ratas control comoobesas. Estos resultados sugieren que los efectosbeneficiosos de la suplementacion de ladieta con AL sobre la ganancia de peso corporalestan mediados, al menos en parte, por lareduccion observada en la ingesta de comida yen la eficiencia metabolica. Ademas, la accioninhibitoria del AL sobre el transporte intestinalde azucares podria explicar, en parte, la menoreficiencia metabolica observada en los animalestratados con AL justificando, por consiguiente,los efectos beneficiosos del AL sobre la obesidad(AU)