Person: Benedí González, Juana María
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First Name
Juana María
Last Name
Benedí González
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Farmacología, Farmacognosia y Botánica
Area
Farmacología
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
Item Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damagein rats and primary cultures of rat hepatocytes(Experimental and Toxicologic Pathology, 2001) Martín-Aragón Álvarez, Sagrario; Heras Polo, Beatriz De Las; Sánchez Reus, María Isabel; Benedí González, Juana MaríaThe purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.Item A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells(International Journal of Molecular Sciences, 2021) Martín-Aragón Álvarez, Sagrario; Bermejo Bescos, María De La Paloma; Benedí González, Juana María; Raposo Simón, Pedro Carlos; Marques, Franklim; Kydonaki, Eirini K.; Gkiata, Paraskevi; Koutedakis, Yiannis; Ntina, Georgia; Carrillo, Andres E.; Amorim, TâniaGlucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.Item A Diet Containing Rutin Ameliorates Brain Intracellular Redox Homeostasis in a Mouse Model of Alzheimer’s Disease(International Journal of Molecular Sciences, 2023) Jiménez-Aliaga, Karim L.; Bermejo Bescos, María De La Paloma; Benedí González, Juana María; Martín-Aragón Álvarez, SagrarioQuercetin has been studied extensively for its anti-Alzheimer’s disease (AD) and anti-aging effects. Our previous studies have found that quercetin and in its glycoside form, rutin, can modulate the proteasome function in neuroblastoma cells. We aimed to explore the effects of quercetin and rutin on intracellular redox homeostasis of the brain (reduced glutathione/oxidized glutathione, GSH/GSSG), its correlation with β-site APP cleaving enzyme 1 (BACE1) activity, and amyloid precursor protein (APP) expression in transgenic TgAPP mice (bearing human Swedish mutation APP transgene, APPswe). On the basis that BACE1 protein and APP processing are regulated by the ubiquitin–proteasome pathway and that supplementation with GSH protects neurons from proteasome inhibition, we investigated whether a diet containing quercetin or rutin (30 mg/kg/day, 4 weeks) diminishes several early signs of AD. Genotyping analyses of animals were carried out by PCR. In order to determine intracellular redox homeostasis, spectrofluorometric methods were adopted to quantify GSH and GSSG levels using o-phthalaldehyde and the GSH/GSSG ratio was ascertained. Levels of TBARS were determined as a marker of lipid peroxidation. Enzyme activities of SOD, CAT, GR, and GPx were determined in the cortex and hippocampus. ΒACE1 activity was measured by a secretase-specific substrate conjugated to two reporter molecules (EDANS and DABCYL). Gene expression of the main antioxidant enzymes: APP, BACE1, a Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), caspase-3, caspase-6, and inflammatory cytokines were determined by RT-PCR. First, overexpression of APPswe in TgAPP mice decreased GSH/GSSG ratio, increased malonaldehyde (MDA) levels, and, overall, decreased the main antioxidant enzyme activities in comparison to wild-type (WT) mice. Treatment of TgAPP mice with quercetin or rutin increased GSH/GSSG, diminished MDA levels, and favored the enzyme antioxidant capacity, particularly with rutin. Secondly, both APP expression and BACE1 activity were diminished with quercetin or rutin in TgAPP mice. Regarding ADAM10, it tended to increase in TgAPP mice with rutin treatment. As for caspase-3 expression, TgAPP displayed an increase which was the opposite with rutin. Finally, the increase in expression of the inflammatory markers IL-1β and IFN-γ in TgAPP mice was lowered by both quercetin and rutin. Collectively, these findings suggest that, of the two flavonoids, rutin may be included in a day-to-day diet as a form of adjuvant therapy in AD.Item Lipoprotein Profile in Aged Rats Fed Chia Oil- or Hydroxytyrosol-Enriched Pork in High Cholesterol/High Saturated Fat Diets(Nutrients, 2018) Santos López, Jorge Arturo; Garcimartín Álvarez, Alba; Bastida Codina, Sara; Bautista Ávila, Mirandeli; González Muñoz, María José; Benedí González, Juana María; Sánchez Muniz, Francisco JoséRestructuring pork (RP) by adding new functional ingredients, like Chia oil (one of the richest natural source of α-linolenic acid) or hydroxytyrosol (HxT) (potent antioxidant), both with hypolipidemic activities, is one of the strategies that may help to reduce the potential negative effects of high meat products consumption. The aim of this study was to evaluate the Chia oil- or HxT-enriched RP effect on the lipoprotein profile of aged rats fed high fat, high-energy, and cholesterol-enriched diets. RP samples were prepared by mixing lean pork and lard with or without Chia oil (152.2 g/kg fresh matter) or HxT (3.6 g/kg fresh matter). Diets were prepared by mixing a semisynthetic diet with freeze-dried RP. Groups of 1-year male Wistar rats were fed the following experimental diets for 8 weeks: C, control-RP diet; HC, cholesterol-enriched-RP diet; and Chia oil-RP (CHIA) and HxT, Chia oil- or hydroxytyrosol-RP, cholesterol-enriched diet. Plasma lipid, lipoprotein profile, SREBP-1c protein, and low-density lipoproteins (LDL) receptor gene (Ldlr) exp essions were evaluated. Compared to C diet, the HC diet increased plasma cholesterol, triglycerides, free fatty acids, total lipids, and SREBP-1c expression, but reduced Ldlr expression and significantly modified the lipoprotein profile, giving rise to the presence of high levels of atherogenic cholesterol enriched very low-density lipoproteins (VLDL) particles. Compared to the HC diet, the HxT diet did not produce significant changes in feed intake but it reduced the body weight. Chia oil and HxT partially arrested the negative effects of the high-fat, high-energy, and cholesterol enriched meat-based diets on lipemia and lipoproteinemia, mostly by reducing the amount of cholesterol content in VLDL (60% and 74% less in CHIA and HxT vs. HC, respectively) and the VLDL total mass (59% and 63% less in CHIA and HxT vs. HC, respectively). Free fatty acids (FFA) significantly correlated with adipose tissue weight and VLDL total mass (both p < 0.05), and plasma triglycerides, phospholipids, total lipids, and SREBP-1c (all p < 0.001), suggesting the important role of FFA in lipoprotein metabolism. Results support the recommendation to include these ingredients in pork products addressed to reduce the presence of increased atherogenic particles in aged people at CVD risk consuming large amounts of pork.Item Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late‐Stage Type 2 Diabetes Mellitus?(Molecular Nutrition & Food Research, 2022) Hernández Martín, Marina; Bocanegra De Juana, Aranzazu; Redondo Castillejo, Rocío; Macho González, Adrián; Sánchez Muniz, Francisco José; Benedí González, Juana María; Bastida Codina, Sara; García Fernández, Rosa Ana; Garcimartín Álvarez, Alba; López-Oliva Muñoz, María ElviraScope: Hypercholesterolemia increases the risk of mortality in type 2 diabetesmellitus (T2DM), especially in the late-stage. Consumption of bioactivecompounds as functional ingredients would help achieve therapeutic goals forcholesterolemia. Silicon has demonstrated a hypocholesterolemic effect andthe ability to reduce fat digestion. However, it is unclear whether silicon exertssuch effect in late-stage T2DM (LD) and the intestinal mechanisms involved.Methods and results: Three groups of eight rats were included: early-stageT2DM control (ED), LD, and the LD group treated with silicon (LD-Si) oncethe rats were diabetic. Morphological alterations of the duodenal mucosa, andlevels of markers involve in cholesterol absorption and excretion, besidecholesterolemia, and fecal excretion were assayed. Silicon included as afunctional ingredient significantly reduces cholesterolemia in part due to: 1)reducing cholesterol intestinal absorption by decreasing the absorptive areaand Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasingcholesterol excretion to the lumen by induction of the liver X receptor (LXR)and consequent increase of adenosine triphosphate-binding cassettetransporter (ABCG5/8).Conclusions: These results provide insight into the intestinal molecularmechanisms by which silicon reduces cholesterolemia and highlights theefficacy of the consumption of silicon-enriched functional foods in late-stageT2DM.