Examinando por Autor "Miguel, Marta"

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Aluminum exposure for 60 days at an equivalent human dietary level promotes peripheral dysfunction in rats
(Elsevier, 2017-08-25) Caroline Silveira Martinez; Uranga, Jose Antonio; Franck Maciel Peçanha; Dalton Valentim Vassallo; Vera, Gema; Miguel, Marta; Giulia Alessandra Wiggers
Aluminum (Al) is a neurotoxic associated with a number of chronic human diseases. We investigated the effects of Al exposure at doses similar to human dietary levels on the peripheral nervous system over a 60 day period. Wistar male rats were divided into two major groups and received orally: 1) Low aluminum level - rats were subdivided and treated for 60 days as follows: a) Untreated - ultrapure water; b) AlCl3 at a dose of 8.3 mg/kg bw for 60 days, representing human Al exposure by diet; and 2) High aluminum level - rats were subdivided and treated for 42 days as follows: C) Untreated – ultrapure water; d) AlCl3 at 100 mg/kg bw for 42 days, representing a high level of human exposure to Al. Von Frey hair and plantar tests were used to verify the tactile and thermal sensitivities, respectively. The presence of catalepsy behavior and the spontaneous motor activity were investigated by “ring test” and using individual photocell activity chambers. Reactive oxygen species, lipid peroxidation and total antioxidant capacity in plasma, were measured. Immunohistochemistry to investigate the nerve inflammation and, the specific presence of Al in the sciatic nerve fibers were investigated. Al exposure at a representative human dietary level promotes the development of mechanical allodynia, catalepsy behavior, increased the number of activated macrophages in the sciatic nerve, systemic oxidative stress and, is able to be retained among the sciatic nerve fibers. The effects of Al in the peripheral nervous system were similar to those found in rats exposed to Al at a dose much higher (100 mg/kg). Therefore, our findings suggest that Al may be considered toxic for the peripheral nervous system, thus inducing peripheral dysfunction.
Ameliorative effects of egg white hydrolysate on recognition memory impairments associated with chronic exposure to low mercury concentration
(Elsevier, 2016-12) Rizzetti, Danize Aparecida; Caroline Dalla Colletta Altermann; Caroline Silveira Martinez; Franck Maciel Peçanha; Dalton Valentim Vassallo; Uranga Ocio, Jose Antonio; Miguel, Marta; Wiggers, Giulia Alessandra; Pâmela Billig Mello-Carpes
The study aimed to investigate if the EWH is able to prevent the recognition memory disorders associated with long-term Hg exposure in rats. For this, male Wistar rats were treated for 60 days with: a) Untreated: saline solution (i.m.); b) Hydrolysate: EWH (1 g/kg/day, gavage); c) Mercury: HgCl2 (1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day, i.m.); d) Hydrolysate-Mercury. Object recognition memory test was performed to verify Short (STM) and Long-Term Memory (LTM) and Open Field, Plus Maze and Tail Flick tests were performed as control for behavioral experiments. Reactive Oxygen Species (ROS) in hippocampus were determined by dichlorofluorescein diacetate (DCFH-DA) method, malondialdehyde (MDA) levels by TBARS, antioxidant power by FRAP assay and total Hg concentration by atomic fluorescence spectrometry. We confirm that the STM and LTM were impaired in adult rats exposed to Hg at low concentrations, which may be related to the increased metal deposition, ROS production and subsequently the oxidative damage in hippocampus. In addition, we demonstrated for the first time that EWH treatment is able to prevent memory impairment induced by Hg exposure, reducing Hg content and ROS production in hippocampus. In conclusion, EWH ameliorates memory impairments induced by chronic exposure to low doses of Hg. These findings may represent a good public health strategy since they indicate that EWH is a promising candidate as a new natural therapy for heavy metals intoxication.
Chronic mercury at low doses impairs white adipose tissue plasticity
(Elsevier, 2019-02-23) Rizzetti, Danize Aparecida; Corrales, Patricia; Piagette, Janaina Trindade; Uranga, Jose Antonio; Vera, Gema; Peçanha, Franck Maciel; Vassallo, Dalton Valentim; Miguel, Marta; Wiggers, Giulia Alessandra
Introduction: The toxic effects of mercury (Hg) are involved in homeostasis of energy systems such as lipid and glucose metabolism, and white adipose tissue dysfunction is considered as a central mechanism leading to metabolic disorders. Objective: The aim of this study was to determine the effects of chronic inorganic Hg exposure at low doses on the lipid and glycemic metabolism. Methods: Male Wistar rats were divided into two groups and treated for 60 days with: saline solution, i.m. (Untreated) and mercury chloride, i.m. - 1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day - (Mercury). Histological analyses, Hg levels measurement and GRP78, CHOP, PPARα, PPARγ, leptin, adiponectin and CD11 mRNA expressions were performed in epididymal white adipose tissue (eWAT). Glucose, triglycerides, total cholesterol and insulin plasma levels were also measured. Results: Hg exposure reduced the absolute and relative eWAT weights, adipocyte size, plasma insulin levels, glucose tolerance, antioxidant defenses and increased plasma glucose and triglyceride levels. In addition, CHOP, GRP78, PPARα, PPARγ, leptin and adiponectin mRNA expressions were increased in Hg-treated animals. No differences in Hg concentration were found in eWAT between the untreated and Hg groups. These results suggest that the reduction in adipocyte size is related to the impaired antioxidant defenses, endoplasmic reticulum (ER) stress, the disrupted PPARs and adipokines mRNA expression induced by the metal in eWAT. These disturbances possibly induced a decrease in circulating insulin levels, an imbalance between lipolysis and lipogenesis mechanisms in eWAT, with an increase in fatty acids mobilization, a reduction in glucose uptake and an activation of pro-apoptotic pathways, leading to hyperglycemia and hyperlipidemia. Conclusions: Hg is a powerful environmental WAT disruptor that influences signaling events and impairs metabolic activity and hormonal balance of adipocytes.
Egg White Hydrolysate as a functional food ingredient to prevent cognitive dysfunction in rats following long-term exposure to aluminum
(Nature, 2019-02-12) Silveira Martinez, Caroline; Alterman, Caroline; Vera, Gema; Márquez, Antonio; Uranga, Jose Antonio; Peçanha, Franck Maciel; Vassallo, Dalton Valentim; Exley, Christopher; Mello-Carpes, Pamela; Miguel, Marta; Wiggers, Giulia
Aluminum (Al), which is omnipresent in human life, is a potent neurotoxin. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against changes in cognitive function in rats exposed to both high and low levels of Al. Indeed, EWH has been previously shown to improve the negative effects induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment (1 g/kg/day). After 60 or 42 days of exposure, rats exposed to Al and EWH did not show memory or cognitive dysfunction as was observed in Al-treated animals. Indeed, co-treatment with EWH prevented catalepsy, hippocampal oxidative stress, cholinergic dysfunction and increased number of activated microglia and COX-2-positive cells induced by Al exposure. Altogether, since hippocampal inflammation and oxidative damage were partially prevented by EWH, our results suggest that it could be used as a protective agent against the detrimental effects of long term exposure to Al.
Egg white hydrolysate promotes neuroprotection for neuropathic disorders induced by chronic exposure to low concentrations of mercury
(Elsevier, 2016-09-01) Rizzetti, Danize Aparecida; Fernández, Francisca; Silvia Moreno; Uranga Ocio, Jose Antonio; Franck Maciel Pecanha; Vera, Gema; Vassallo, Dalton Valentim; Miguel, Marta; Wiggers, Giulia Alessandra
This study aims to investigate whether the egg white hydrolysate (EWH) acts on the neuropathic disorders associated with long-term Mercury (Hg) exposure in rats. 8-week-old male Wistar rats were treated for 60 days with: a) Control - saline solution (i.m.); b) Mercury - HgCl2 (1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day, i.m.); c) Hydrolysate - EWH (1 g/kg/day, gavage); d) Mercury and Hydrolysate. Mechanical allodynia was assessed using Von Frey Hairs test; heat hyperalgesia by the plantar test; catalepsy by a modification of the “ring test” and spontaneous locomotor activity by a photocell activity chambers. Analyses were performed at 0, 30 and 60 days of treatment. Brain and plasma MDA, plasma NPSH and TNF-α determination and skin immunohistochemistry were performed at 60 days. Hg induced a reduction in mechanical sensitivity threshold at 30 and 60 days and in thermal sensitivity threshold at 60 days. At the end of treatment catalepsy was developed, but there was not significant alteration in spontaneous locomotor activity. Hg also increased brain and plasma MDA, plasma NPSH and TNF- α levels and the number of Merkel cell–neurite complex in the skin. EWH prevented the development of mechanical allodynia, thermal hyperalgesia and catalepsy induced by Hg and the increase in MDA concentration in brain and plasma and in the number of Merkel cell–neurite complex in the skin. In conclusion, EWH promotes neuroprotection against the toxic effects caused by Hg, demonstrating a beneficial therapeutic potential.
Egg white hydrolysates improve vascular damage in obese Zucker rats by its antioxidant properties
(Wiley Online Library, 2019-10-01) Garcés-Rimón, Marta; Cristina González; Raquel Hernanz; Esperanza Herradón; Angela Martín; Roberto Palacios; María Jesús Alonso; Uranga, Jose Antonio; López Miranda, Visitación; Miguel, Marta
Metabolic Syndrome (MS) is related to increased risk of early death due to cardiovascular complications, among others. Dietary intervention has been suggested as the safest and most cost‐effective alternative for treatment of those alterations in patients with MS. The aim of this study was to investigate the effects of different egg white hydrolysates (HEW1 and HEW2) in obese Zucker rats, focus on the development of cardiovascular complications. Blood pressure, heart rate, basal cardiac function and vascular reactivity in aorta and mesenteric resistance arteries were evaluated. Reactive oxygen species production by dihydroethidium‐emitted fluorescence, NOX‐1 mRNA levels by qRT‐PCR, angiotensin‐converting enzyme activity by fluorimetry and kidney histopathology were also analysed. Both hydrolysates improve the endothelial dysfunction occurring in resistance arteries. Additionally, HEW2 reduced vascular oxidative stress. Practical applications Egg white is a good source of bioactive peptides, some of them with high antioxidant activity. They may be used as functional foods ingredients and could serve as an alternative therapeutic option to decrease some Metabolic Syndrome‐related complications. This study suggests that these hydrolysates could be an interesting nonpharmacological tool to control cardiovascular complications related to Metabolic Syndrome.
Expression enhancement in brown adipose tissue of genes related to thermogenesis and mitochondrial dynamics after administration of pepsin egg white hydrolysate
(2018) Moreno-Fernández, Silvia; Garcés-Rimón, Marta; Uranga, Jose Antonio; Julien, Astier; Landrier, JF; Miguel, Marta
Nutritional compounds could be a safe and less expensive treatment for complications associated with obesity and metabolic syndrome (MetS). The aim of this study was to investigate the mechanism of action and the target tissues of a pepsin egg white hydrolysate (EWH) which had previously been demonstrated to improve some obesity-related disorders on a high-fat/high-glucose rat model. Wistar rats were used and divided into 3 groups: Control group (C), High-fat/high-glucose diet (MS) and high-fat/high-glucose diet + EWH (MSH). The rats were fed for 20 weeks and the EWH was administered from the 9th week. At the end of the study, white adipose tissue (WAT), brown adipose tissue (BAT) and muscle samples were collected for RT-qPCR analyses and immunohistochemistry. Our results showed a gene expression enhancement (2-fold basal level) in BAT of genes related to thermogenesis and mitochondrial dynamics. Mitochondrial DNA quantification and immunohistochemistry results also showed an increase of the mitochondrial content in this tissue. In conclusion, our results show the potential metabolic effect of this pepsin EWH by enhancing mitochondrial proliferation and gene expression related to thermogenesis in BAT. The EWH could be used as a functional food ingredient which is able to increase energy expenditure and counteract obesity-related MetS in a chronically obese society.
Pepsin egg white hydrolysate ameliorates metabolic syndrome in high-fat/high-dextrose fed rats.
(Royal Society of Chemistry, 2018) Moreno-Fernández, Silvia; Garcés-Rimón, Marta; González, Cristina; Uranga, Jose Antonio; López Miranda, Visitación; Vera, Gema; Miguel, Marta
The aim of this study was to examine the effect of a pepsin egg white hydrolysate (EWH) on metabolic complications using a high-fat/high-dextrose diet-induced Metabolic Syndrome (MetS) experimental model. Male Wistar rats where divided in 4 groups which received: standard diet and water (C), standard diet and a solution with 1g/kg/day of EWH (CH), high-fat/high-dextrose diet and water (MS), and high-fat/high-dextrose diet and a solution with 1g/kg/day of EWH (MSH). EWH consumption normalized body weight gain, the abdominal obesity and the peripheral neuropathy developed in MetS animals, reduced adipose tissue and liver weight, as well as plasma glucose. Oxidative stress and inflammation biomarkers were normalized in MSH animals. In conclusion oral administration of EWH could be used as a functional food ingredient to improve some complications associated to MetS induced by unhealthy diets
Pepsin Egg White Hydrolysate Improves Glucose Metabolism Complications Related to Metabolic Syndrome in Zucker Fatty Rats
(MDPI, 2018-04-03) Garcés, Marta; González, Cristina; Uranga, Jose Antonio; López Miranda, Visitación; Vera, Gema; Miguel, Marta; Lopez Fandiño, Rosina
The purpose of this study was to evaluate the effect of the administration of two egg white hydrolysates on glucose metabolism complications related to Metabolic Syndrome (MS) in Zucker fatty rats (ZFR). ZFR were given 750 mg/kg/day of egg white hydrolyzed with pepsin (HEW1) or with aminopeptidase (HEW2) for 12 weeks in their drinking water or just water. Zucker lean rats (ZLR), which received water, were used as a control. The presence of tactile allodynia, which is a sign of peripheral neuropathy, was assessed. Blood samples and pancreas were collected to determine the effect of the hydrolysates on glucose metabolism. The intake of HEW1 significantly lowered plasma insulin levels and improved the quantitative indexes of insulin resistance, insulin sensitivity, and pancreatic _-cell functionality (HOMA-IR, HOMA-_, and QUICKI, respectively), but non-significant changes were observed in group treated with HEW2. Compared to ZLR, ZFR showed tactile allodynia, but the consumption of both hydrolysates significantly increased mechanical sensitivity in ZFR. In conclusion, HEW1 pepsin could improve the glucose metabolism abnormalities associated with MS in obese Zucker rats.
Potential benefits of egg white hydrolysate in the prevention of Hg-induced dysfunction in adipose tissue
(2022) Danize Aparecida Rizzetti; Patricia Corrales; Uranga, Jose Antonio; Gema Medina-Gómez; Franck Maciel Peçanha; Dalton Valentim Vassallo; Miguel, Marta; Giulia Alessandra Wiggers
Aim: To investigate the effects of egg white hydrolysate (EWH) on the lipid and glycemic metabolism disruption in the white adipose tissue (WAT) dysfunction induced by mercury (Hg). Experimental: Wistar rats were treated for 60 days: control (saline, intramuscular – i.m.); hydrolysate (EWH, gavage, 1 g kg−1 day−1); mercury (HgCl2, i.m., 1st dose 4.6 μg kg−1, subsequent doses 0.07 μg kg−1 day−1) and hydrolysate-mercury (EWH-HgCl2). Hg level and histological analyses were performed in epididymal WAT (eWAT), pancreas and liver. GRP78, CHOP, PPARα, PPARγ, leptin, adiponectin, and CD11 mRNA expressions were analyzed in eWAT. The plasma lipid profile, glucose, and insulin levels were measured. Antioxidant status was also evaluated in the plasma and liver. Results: EWH intake prevented the reduced eWAT weight, adipocyte size, insulin levels, and antioxidant defenses and the increased glucose and triglyceride levels induced by Hg exposure; hepatic glutathione levels were higher in rats co-treated with EWH. The increased mRNA expression of CHOP, PPARα, and leptin induced by Hg was reduced in co-treated rats. EWH did not modify the elevated mRNA expression of GRP78, PPARγ and adiponectin in Hg-treated rats. Increased levels of Hg were found in the liver; the co-treatment did not alter this parameter. EWH prevented the morphological and metabolic disorder induced by Hg, by improving antioxidant defenses, inactivating pro-apoptotic pathways and normalizing the mRNA expression of PPARs and adipokines. Its effects enabled an increase in insulin levels and a normal balance between the fat storage and expenditure mechanisms in WAT. Conclusions: EWH may have potential benefits in the prevention and management of Hg-related metabolic disorders.