Study of the metabolic impact of hyperlipemic diets in monomorfonuclear cells of peripheral blood: preliminary results

Las alteraciones metabólicas asociadas a la dieta son de gran impacto en la salud, ya que se encuentran relacionadas con enfermedades crónicas no transmisibles, tales como obesidad, enfermedades cardiovasculares, diabetes, entre otras. Las células monomorfonucleares sanguíneas (PBMC) constituyen un rol importante como biomarcadores tempranos en el estudio del impacto de dietas enriquecidas en grasas sobre el metabolismo lipídico. Estas permiten profundizar el conocimiento de la patogenia por métodos no invasivos de manera precoz. Por lo que el objetivo planteado es estudiar las PBMC como una herramienta de investigación de la expresión génica en alteraciones del metabolismo lipídico

Efecto de la dieta hiperlipemica sin suplementación de carbohidratos sobre el tejido hepático en conejos adultos neozelandeses

Las dislipidemias adquiridas se asocian a diversos trastornos metabólicos como diabetes mellitus, obesidad y síndrome metabólico. Si bien en algunos casos se conocen los mecanismos que los generan aún no está claro el de algunas de ellas. El objetivo de la presente investigación fue desarrollar un modelo experimental de dislipidemia inducida por una dieta lipídica sin carbohidratos añadidos. Esto nos permite analizar parámetros bioquímicos y tisulares sin generar un modelo de Síndrome Metabólico (SM). El modelo animal, conejos machos adultos de Nueva Zelanda, permite evaluar los cambios en la dieta a lo largo del tiempo. Los animales fueron alimentados durante 12 meses en cuatro trimestres (I, II, III y IV). En I, los animales fueron alimentados con una dieta estándar para conejos. En II, se añadió N: 7 14% de grasa bovina (G) y N: 2 con 14% de aceite de oliva (AO). N:2 siguieron con alimentación estándar (grupo C). En III, N: 3 comenzó a consumir solo el 7% de G (MG) y N: 4 continuó con G hasta el final del experimento. En IV el MG consumió 4% de G con 4% de AO (MGAO)

Polymeric Nanomicelles Loaded with Anandamide and Their Renal Effects as a Therapeutic Alternative for Hypertension Treatment by Passive Targeting

We have previously demonstrated significant in vitro natriuretic effects of anandamide (AEA) nanoformulation in polymeric nanoparticles, whose size prevents their accumulation in organs, such as the kidneys. Therefore, it is of particular interest to design and test nanostructures that can pharmacologically accumulate in these organs. In this regard, we prepared and characterized polymeric nanomicelles (~14 and 40 nm). Likewise, their biodistribution was determined. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), n = 3 per group, were divided into five treatment conditions: control, sham, free AEA freshly dispersed in aqueous solution or 24 h after its dispersion, and AEA encapsulated in nanomicelles. The kidneys were the main site of accumulation of the nanoformulation after 24 h. Freshly dispersed free AEA showed its classical triphasic response in SHR, which was absent from all other treatments. Nanoformulated AEA produced a sustained antihypertensive effect over 2 h, accompanied by a significant increase in fractional sodium excretion (FSE %). These effects were not observed in WKY, sham, or free AEA-treated rats after 24 h of its aqueous dispersion. Without precedent, we demonstrate in vivo natriuretic, diuretic, and hypotensive effects of AEA nanoformulation in polymeric nanomicelles, suggesting its possible use as a new antihypertensive agent with intravenous administration and passive renal accumulation

Angiotensin AT1 receptor inhibition-induced apoptosis by RhoA GTPase activation and pERK1/2 signaling pathways in neonatal obstructive nephropathy

Intrarenal renin-Angiotensin system (RAS) activity is increased during early development and is further enhanced by unilateral ureteral obstruction (UUO). We studied the involvement of mitogen-activated protein (MAP) kinase members and the RhoA GTPase signaling pathways on the regulation of renal cell response after AT1 Angiotensin II receptor inhibition in obstruction. Neonatal rats subjected to sham operation or complete UUO within the first 48 hours of life received saline vehicle, Losartan (AT1 inhibitor), or PD-123319 (AT2 inhibitor) during the first 14 days of life. Cortex tubular epithelial cell apoptotic response was shown by TUNEL and confirmed by electron microscopy associated with mitochondrial signaling pathway through the increased proapoptotic ratio Bax/BcL-2, and consequently increased caspase 3 expression and activity in obstructed kidney before and after Type 1 (AT1) receptor blockade. Non injury of contralateral kidney was shown. The convergence of two independent signal pathways, the RhoA GTPase and pERK and concurrent inhibition of JNK MAP kinase, were required for the apoptotic response in 14 day kidney obstructed tubular cells either with or without Losartan treatment. Absence of increased AT2 protein expression after AT1 receptor inhibition on day 14 of obstruction was shown. Selective AngiotensinAT2-receptor inhibition with PD-123319 had no protective effect on the renal response to complete 14 day UUO. We suggest a role of both RhoA GTPase activation and the opposing actions of the ERK and JNK-MAP kinase signaling pathways as events involved in tubular cell apoptosis regulation in neonatal UUO. The selective AT1-receptor inhibition had no effect on the renal cellular response in the kidney subjected to UUO for 14 days

Additional file 1: Data S1. of Changes in renal WT-1 expression preceding hypertension development

RT-PCR expression in SHRs cortex kidney. Representative gel of WT-1, VDR, Hsp70 and AT1 mRNA expression in SHRs cortex kidney. Housekeeping gene β-actin expression is shown in the line here below. (TIF 26384 kb