Differential effects of hypo- and hyperthyroidism on remodeling of contacts between neurons expressing the neuropeptide EI and tyrosine hydroxylase in hypothalamic areas of the male rat.

The Neuropeptide EI (NEI, glutamic acid- isoleucine amide) participates in neuroendocrine function. Previously we demonstrated that NEI concentration is regulated by thyroid hormones in discrete hypothalamic areas in rats. We observed that the thyroid status affects the dopaminergic regulation of the pituitary hormones. In this study we explored possible interactions between NEI and tyrosine hydroxylase (TH) containing elements in selected hypothalamic areas of male rats. Neuronal somas, terminals and boutons were assessed by confocal microscopy, in hypo- and hyperthyroid animals. We observed a remodeling of the contacts between the TH and NEI immunoreactive elements in the incerto-hypothalamic area (IHy, also known as rostromedial zona incerta) according to thyroid function. However, in the dorsolateral zone of the peduncular part of the lateral hypothalamus (DL-PLH) the thyroid hormones affect the dendritic trees of the neurons without perturbing the overall NEI/TH contacts. Also, we demonstrated that TRH Receptor 1 (TRH-R1) is colocalized in NEI immunoreactive neurons in the peduncular part of the lateral hypothalamus (PLH) and NEI precursor mRNA expression increased by hypothyroidism indicating that NEI neurons are responsive to the feedback mechanisms of the Hypothalamic Pituitary-Thyroid Axis (HPT). In conclusion, the hypothyroid status seems to increase the interactions between the NEI neurons and the dopaminergic pathways while hyperthyroidism either decreases or displays no effects. Altogether these observations support the participation of the IHy and PLH NEI as a modulating component of the HPT suggesting that altered neuroendocrine, behavioral and cognitive dysfunctions induced by dysthyroidism could be in part mediated by NEI.

Bioaccessibility during In Vitro Digestion and Antiproliferative Effect of Bioactive Compounds from Andean Berry ( Vaccinium meridionale Swartz) Juice.

Berry consumption is associated with colorectal-cancer chemoprevention, but digestive conditions can affect this property. The bioaccessibility and apparent permeability coefficients of bioactive compounds from Andean Berry Juice (ABJ) after in vitro gastrointestinal digestion and colonic fermentation were analyzed. The antiproliferative effect of the fermented nondigestible fraction was evaluated against SW480 colon-adenocarcinoma cells. Gallic acid displayed the highest bioaccessibility in the mouth, stomach, small intestine, and colon. However, chlorogenic acid exhibited the highest apparent permeability coefficients (up to 1.98 × 10-4 cm/s). The colonic-fermentation fraction showed an increase of ≥50% antiproliferative activity against SW480 cells (19.32%, v/v), equivalent to those of gallic acid (13.04 µg/g), chlorogenic acid (7.07 µg/g), caffeic acid (0.40 µg/g), ellagic acid (7.32 µg/g), rutin (6.50 µg/g), raffinose (0.14 mg/g), stachyose (0.70 mg/g), and xylose (9.41 mg/g). Bioactive compounds from ABJ are bioaccessible through the gastrointestinal tract and colon fermentation, resulting in antiproliferative activity.

Free radical scavenging capacity and cytotoxic and antiproliferative effects of Vaccinium meridionale Sw. agains colon cancer cell lines / Capacidad atrapadora de radicales libres, efectos citotóxicos y antiproliferativos de Vaccinium meridionale Sw. en líneas celulares de cáncer de colon

Introduction: Vaccinium meridionale Swartz, of the family Ericaceae, is commonly known as mortiño or agraz. The plant is considered a functional food, with a content of anthocyanins and antioxidants similar to or greater than that reported for other Vaccinium species. However, little is known about its nutraceutical and medicinal properties. Objectives: determine the antioxidant activity and cytotoxic and antiproliferative effect of mortiño fruit aqueous extract against colon adenocarcinoma cells (SW480) and their derived metastatic cells (SW620). Methods: total phenols and anthocyanins were determined by the Folin-Ciocalteu method. Caffeoyl derivatives were determined by HPLC-DAD. Antioxidant activity was analyzed as the ability to scavenge reactive oxygen species (ROS), reactive nitrogen species (RNI), peroxyl radicals and hydroxyl radicals. Cytotoxic and antiproliferative activities were studied by MTT and sulforhodamine B. Results: the following substances were found in 100 g of lyophilized extract: total phenols (2 546 mg GAE), anthocyanins (150.7 mg C3G), chlorogenic acid (126 mg), ferulic acid (108 mg) and coumaric acid (63 mg). Hydroxyl radical scavenging capacity was 36 147.5 ?mol DMSO, whereas ROS and RNS scavenging capacity was 29 255.9 y 41 775.2 ?molTrolox, respectively. ORAC value was 41 775.2 ?molTrolox. A dose-dependent cytotoxic and antiproliferative effect was observed. IC50 value was 59.12 µg/ml for SW480 and 56.10 µg/mL for SW620. Conclusions: mortiño fruit aqueous extract exhibited antioxidant, cytotoxic and antiproliferative activities comparable to those of other berries of the genus Vaccinium, which could be partly explained by the presence of a high content of anthocyanins and phenolic acids.

Introducción: Vaccinium meridionale Swartz, pertenece a la familia Ericaceae, conocida comúnmente como mortiño agraz. Considerado un alimento funcional por su contenido de antocianinas y antioxidantes similares o mayor al reportado para otras especies de Vaccinium. Sin embargo, poco se conoce sobre sus propiedades nutracéuticas y en la salud. Objetivos: determinar en extracto acuoso del fruto mortiño, la actividad antioxidante y su efecto citotóxico y antiproliferativo en células de adenocarcinoma de colon (SW480) y sus derivadas metastásicas (SW620). Métodos: contenido de fenoles y antocianinas totales se determinó por el método Folin-Ciocalteu, los derivados caffeoil por HPLC-DAD. La actividad antioxidante se analizó como habilidad para atrapar especies reactivas del oxígeno (ROS) y del nitrógeno (RNI), radicales peróxilo e hidróxilo. La actividad citotóxica y antiproliferativa se estudiaron por MTT y sulforodamina B. Resultados : en 100 g de liofilizado se encontrófenoles totales (2546 mg GAE), antocianinas (150,7 mg C3G), ácido clorogénico (126 mg), ácido ferúlico (108 mg) y cumárico (63 mg), capacidad atrapadora de radical hidroxilo fue 36147,5 ?mol DMSO, capacidad atrapadorade ROS y RNS fue 29255,9 y 41775,2 ?mol Trolox, respectivamente, valor ORAC 41775,2 ?mol Trolox. Se observó un efecto citotóxico y antiproliferativo dosis-dependiente. El valor IC50 para SW480: 59,12 µg/mL y SW620: 56,10 µg/mL. Conclusiones: el extracto acuoso del fruto del mortiño exhibió actividades antioxidantes, citotóxicas y antiproliferativas comparables a las de otras bayas del género Vaccinium, lo que podría ser explicado parcialmente por la presencia del alto contenido de antocianinas y ácidos fenólicos.