Garlic and Onion Attenuates Vascular Inflammation and Oxidative Stress in Fructose-Fed Rats

This study evaluates the antioxidant and the anti-inflammatory properties of garlic (G) and onion (O) in fructose-fed rats (FFR). Thirty-day-old male Wistar rats were assigned to control (C), F (10% fructose in drinking water), F+T (tempol 1 mM as control antioxidant), F+G, and F+O. Aqueous G and O extracts were administered orally in doses of 150 and 400 mg/kg/d respectively, and along with tempol, were given during the last 8 weeks of a 14-week period. At the end of the study, FFR had developed insulin resistance, aortic NADPH oxidase activity, increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1) expression in mesenteric arteries, and a decrease in heart endothelial nitric oxide synthase (eNOS). Garlic and onion administration to F rats reduced oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression. These results provide new evidence showing the anti-inflammatory and antioxidant effect of these vegetables

Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet

An impaired capacity of adipose tissue expansion leads to adipocyte hypertrophy, inflammation and insulin resistance (IR) under positive energy balance. We previously showed that a grape pomace extract, rich in flavonoids including quercetin (Q), attenuates adipose hypertrophy. This study investigated whether dietary Q supplementation promotes adipogenesis in the epididymal white adipose tissue (eWAT) of rats consuming a high-fat diet, characterizing key adipogenic regulators in 3T3-L1 pre-adipocytes. Consumption of a high-fat diet for 6 weeks caused IR, increased plasma TNFα concentrations, eWAT weight, adipocyte size and the eWAT/brown adipose tissue (BAT) ratio. These changes were accompanied by decreased levels of proteins involved in angiogenesis, VEGF-A and its receptor 2 (VEGF-R2), and of two central adipogenic regulators, i.e. PPARγ and C/EBPα, and proteins involved in mature adipocyte formation, i.e. fatty acid synthase (FAS) and adiponectin. Q significantly reduced adipocyte size and enhanced angiogenesis and adipogenesis without changes in eWAT weight and attenuated systemic IR and inflammation. In addition, high-fat diet consumption increased eWAT hypoxia inducible factor-1 alpha (HIF-1α) levels and those of proteins involved in adipose inflammation (TLR-4, CD68, MCP-1, JNK) and activation of endoplasmic reticulum (ER) stress, i.e. ATF-6 and XBP-1. Q mitigated all these events. Q and quercetin 3-glucoronide prevented TNFα-mediated downregulation of adipogenesis during 3T3-L1 pre-adipocytes early differentiation. Together, Q capacity to promote a healthy adipose expansion enhancing angiogenesis and adipogenesis may contribute to reduced adipose hypertrophy, inflammation and IR. Consumption of diets rich in Q could be useful to counteract the adverse effects of high-fat diet-induced adipose dysfunction.Fil: Perdicaro, Diahann Jeanette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Rodriguez Lanzi, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gambarte Tudela, Julian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Miatello, Roberto Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Oteiza, Patricia Isabel. University of California. Departments of Nutrition and Environmental Toxicology; Estados UnidosFil: Vazquez, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina; Argentin

(-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress

We investigated the capacity of dietary (-)-epicatechin (EC) to mitigate insulin resistance through the modulation of redox-regulated mechanisms in a rat model of metabolic syndrome (MetS). Adolescent rats were fed a regular chow diet without or with high fructose (HFr) (10% (w/v)) in drinking water for 8 weeks, and a group of HFr-fed rats was supplemented with EC in the diet. HFr-fed rats developed insulin resistance which was mitigated by EC supplementation. Accordingly, the activation of components of the insulin signaling cascade (insulin receptor (IR), IRS-1, Akt and ERK1/2) was impaired, while negative regulators (PKC, IKK, JNK and PTP1B) were upregulated in the liver and adipose tissue of HFr rats. These alterations were partially or totally prevented by EC supplementation. In addition, EC inhibited events which contribute to insulin resistance: HFr-associated increased expression and activity of NADPH oxidase , activation of redox-sensitive signals , expression of NF-kB-regulated pro-inflammatory cytokines and chemokines, and some sub-arms of endoplasmic reticulum stress signaling. Collectively, these findings indicate that EC supplementation can mitigate HFr-induced insulin resistance and are relevant to define interventions that can prevent/mitigate MetS-associated insulin resistance.Fil: Bettaieb, Ahmed. University of California at Davis; Estados UnidosFil: Vazquez, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Rodriguez Lanzi, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Miatello, Roberto Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Haj, Fawaz G.. University of California at Davis; Estados UnidosFil: Fraga, César Guillermo. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Grape pomace and grape pomace extract improve insulin signaling in high-fat-fructose fed rat-induced metabolic syndrome

In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro-inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds.Fil: Rodriguez Lanzi, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Perdicaro, Diahann Jeanette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Antoniolli, Andrea Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Fontana, Ariel Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Miatello, Roberto Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Bottini, Ambrosio Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Vazquez, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Grape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes

This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar–Kyoto (WKY) rats fed a high-fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e., peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue “browning,” i.e., PPARγ-coactivator-1α (PGC-1α), PPARγ PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 up-regulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate, the addition of GPE (30 μM) activated the β-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated up-regulation of proteins involved in mitochondrial biogenesis (PGC-1α PPARγ PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (−)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction.Fil: Rodriguez Lanzi, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Perdicaro, Diahann Jeanette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Fontana, Ariel Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Antoniolli, Andrea Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Miatello, Roberto Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Oteiza, Patricia Isabel. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vazquez, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

A ketogenic diet in combination with gemcitabine increases survival in pancreatic cancer KPC mice

Pancreatic ductal adenocarcinoma (PDAC) continues to be a major health problem. A ketogenic diet (KD), characterized by a very low carbohydrate and high fat composition, has gained attention for its anti-tumor potential. We evaluated the effect and mechanisms of feeding a strict KD alone or in combination with gemcitabine in the autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. For this purpose, both male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD; %kcal: 70% carb, 14% protein, 16% fat), a KD (%kcal: 14% protein, 1% carb, 85% fat), a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. Mice fed a KD alone or in combination with gemcitabine showed significantly increased blood β-hydroxybutyrate levels compared to mice fed a CD or CG. KPC mice fed a KG had a significant increase in overall median survival compared to KPC mice fed a CD (increased overall median survival by 42%). Interestingly, when the data was disaggregated by sex, the effect of a KG was significant in female KPC mice (60% increase in median overall survival), but not in male KPC mice (28% increase in median overall survival). Mechanistically, the enhanced survival response to a KD combined with gemcitabine was multifactorial, including inhibition of ERK and AKT pathways, regulation of fatty acid metabolism and the modulation of the gut microbiota. In summary, a KD in combination with gemcitabine appears beneficial as a treatment strategy in PDAC in KPC mice, deserving further clinical evaluation

Phospho-Aspirin (MDC-22) inhibits pancreatic cancer growth in patient-derived tumor xenografts and KPC mice by targeting EGFR: Enhanced efficacy in combination with irinotecan.

Novel therapeutic strategies are needed in the fight against pancreatic cancer. We have previously documented the chemopreventive effect of MDC-22 in preclinical models of pancreatic cancer. In the present work, we examined the therapeutic effects of MDC-22 in patient-derived tumor xenografts (PDTXs) and in LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre (KPC) genetically engineered mice, two complementary and clinically relevant animal models of pancreatic cancer. In addition, we evaluated whether MDC-22 could synergize with current chemotherapeutic drugs used in the clinic. MDC-22 reduced the growth of various human pancreatic cancer cell lines in a concentration-dependent manner. In vivo, MDC-22 strongly reduced patient-derived pancreatic tumor xenograft growth by 50%, and extended survival of LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mice by over a month (5.3 months versus 7.0 months). In both models, MDC-22 inhibited EGFR activation and its downstream signals, including ERK and FAK phosphorylation. In human pancreatic cancer cell lines, MDC-22 enhanced the growth inhibitory effect of irinotecan, and to a lesser degree those of gemcitabine and nab-paclitaxel. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of, both, MDC-22 alone or in combination with irinotecan, indicating selectivity. Furthermore, MDC-22 enhanced irinotecans effect on cell migration, in part, by inhibiting EGFR/FAK signaling. Collectively, our results indicate that MDC-22 is an effective anticancer drug in preclinical models of pancreatic cancer, and suggest that MDC-22 plus irinotecan as drug combination strategy for pancreatic cancer treatment, which warrants further evaluation

Dietary (-)-epicatechin affects NF-kappa;B activation and NADPH oxidases in the kidney cortex of high-fructose-fed rats

Inflammation involves the activation of redox-sensitive transcription factors, e.g., nuclear factor κB (NF-κB). Administration of (−)-epicatechin to high-fructose-fed rats prevented NF-κB activation and up-regulation of the NADPH oxidase 4 (NOX4) in the kidney cortex. These results add mechanistic insights into the action of (−)-epicatechin diminishing inflammatory responses.Fil: Prince, Paula Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Rodriguez Lanzi, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaFil: Fraga, César Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Galleano, Mónica Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentin

Hepatic safety profile of pancreatic cancer‑bearing mice fed a ketogenic diet in combination with gemcitabine

Ketogenic diets (KDs) are actively being evaluated for their potential anticancer effects. Although KDs are generally considered safe, their safety profile when combined with chemotherapy remains unknown. It is known that a KD enhances the anticancer effect of gemcitabine (2',2'-difluoro-2'-deoxycytidine) in LSL-KrasLSL-G12D/+Trp53R172H/+Pdx-1-Cre (KPC) tumor-bearing mice. In the present study, whether a KD in combination with gemcitabine affected the liver safety profile in KPC mice was evaluated. For this purpose, male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD; % kcal: 20% fat, 65% carbohydrate, 15% protein) + gemcitabine [control plus gemcitabine group (CG)] or a KD (% kcal: 84% fat, 15% protein, 1% carbohydrate) + gemcitabine [ketogenic plus gemcitabine group (KG)] for two months. After two months of treatment, no significant differences in body weight were observed between CGs and KGs. Moreover, the KD did not significantly alter the serum protein expression levels of liver enzymes, including aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. In addition, the KD did not alter markers of liver-lipid accumulation as well as serum cholesterol and triglyceride levels, compared with the CG-treated group. Upon histologic examination, steatosis was rare, with no notable differences between treatment groups. When examining liver fatty acid composition, KD treatment significantly increased the content of saturated fatty acids and significantly decreased levels of cis-monounsaturated fatty acids compared with the CG. Finally, the KD did not affect liver markers of inflammation and oxidative stress, nor the protein expression levels of enzymes involved in ketone bodies, such as 3-hydroxy-3-methylglutaryl-CoA lyase and hidroximetilglutaril-CoA sintasa, and glucose metabolism, such as hexokinase 2, pyruvate dehydrogenase and phosphofructokinase. In summary, a KD in combination with gemcitabine appears to be safe, with no apparent hepatotoxicity and these data support the further evaluation of a KD as an adjuvant dietary treatment for pancreatic cancer

Grape pomace extract supplementation activates FNDC5/irisin in muscle and promotes white adipose browning in rats fed a high-fat diet

Irisin is a myokine regulated by peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) in the exercising skeletal muscle and released into the bloodstream after cleavage of FNDC5. Circulating irisin can up-regulate UCP-1 expression in white adipose tissue (WAT) promoting the formation of brown-like adipocytes. The aim of this study was to evaluate if supplementation with a grape pomace extract (GPE) could activate the FNDC5/irisin pathway via PGC-1α in rats fed a high fat diet (HFD). For this purpose we characterized the activation of: i. the FNDC5/irisin pathway and AMPK in skeletal muscle and ii. proteins involved in the formation of brown-like cells in epididymal WAT (eWAT). Consumption of the GPE activated the FNDC5/irisin pathway, increased AMPK phosphorylation in skeletal muscle and enhanced irisin plasma levels. In eWAT, the GPE increased the level of proteins involved in WAT browning, i.e. PGC-1α, PPARγ, PRDM16 and UCP-1. The GPE also prevented HFD-induced adipocyte hypertrophy and systemic insulin resistance. Consistently, in L6 myotubes, (?)-epicatechin (EC), a flavonoid abundant in the GPE, prevented palmitate-mediated downregulation of FNDC5/irisin protein expression and secretion, in part via PGC-1α activation. Consumption of the GPE, a winemaking residue rich in bioactive compounds, could be a beneficial strategy to counteract the adverse effects of Western style diets through the promotion of WAT browning.Fil: Rodriguez Lanzi, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Perdicaro, Diahann Jeanette. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Gambarte Tudela, Julián. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Muscia Saez, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Fontana, Ariel Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Oteiza, Patricia Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California; Estados UnidosFil: Vazquez, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentin