RESUMO
The purpose of this study was to investigate the effect of an egg white hydrolysate (EWH) to protect white adipose tissue damage from cardiometabolic changes induced by severe hypertension. Male Wistar rats were uninephrectomised and divided: SHAM (weekly subcutaneous vehicle (mineral oil + propylene glycol, 1:1)), SHAM + EWH (subcutaneous vehicle plus EWH via gavage, 1 g/kg per day), DOCA (deoxycorticosterone acetate diluted in vehicle subcutaneously weekly in subsequent doses of 20 mg/kg -1st week, 12 mg/kg - 23th week, and 6 mg/kg -48th week, respectively, plus 1 % NaCl and 0·2 % KCl in drinking water), and DOCA + EWH. Body weight gain, food and water intake, glucose and lipid metabolism were evaluated. Oxidative stress was assessed by biochemical assay and immunofluorescence for NOX-1, nuclear factor kappa B (NFκB), and caspase-3 in retroperitoneal white adipose tissue (rtWAT). Proinflammatory cytokines (IL-6 and 1ß), CD163+ macrophage infiltration, and immunohistochemistry for TNFα and uncoupling protein-1 were evaluated, as well as histological analysis on rtWAT. Glutathione peroxidase and reductase were also determined in plasma. EWH showed hypocholesterolemic, antioxidant, anti-inflammatory, and anti-apoptotic properties in the arterial hypertension DOCA-salt model. The results demonstrated the presence of functional changes in adipose tissue function by a decrease in macrophage infiltration and in the fluorescence intensity of NFκB, NOX-1, and caspase-3. A reduction of proinflammatory cytokines and restoration of antioxidant enzymatic activity and mitochondrial oxidative damage by reducing uncoupling protein-1 fluorescence intensity were also observed. EWH could be used as a potential alternative therapeutic strategy in the treatment of cardiometabolic complications associated with malignant secondary arterial hypertension.
Assuntos
Tecido Adiposo Branco , Acetato de Desoxicorticosterona , Clara de Ovo , Estresse Oxidativo , Ratos Wistar , Animais , Masculino , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Clara de Ovo/química , Ratos , Hipertensão/metabolismo , Hipertensão/induzido quimicamente , Hidrolisados de Proteína/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacosRESUMO
We aimed to investigate whether the consumption of Egg White Hydrolysate (EWH) acts on nervous system disorders induced by exposure to Cadmium (Cd) in rats. Male Wistar rats were divided into (a) Control (Ct): H2O by gavage for 28 days + H2O (i.p. - 15th - 28th day); (b) Cadmium (Cd): H2O by gavage + CdCl2 - 1 mg/kg/day (i.p. - 15th - 28th day); (c) EWH 14d: EWH 1 g/kg/day by gavage for 14 days + H2O (i.p.- 15th - 28th day); (d) Cd + EWH cotreatment (Cd + EWHco): CdCl2 + EWH for 14 days; (e) EWH 28d: EWH for 28 days; (f) EWHpre + Cd: EWH (1st - 28th day) + CdCl2 (15th - 28th day). At the beginning and the end of treatment, neuromotor performance (Neurological Deficit Scale); motor function (Rota-Rod test); ability to move and explore (Open Field test); thermal sensitivity (Hot Plate test); and state of anxiety (Elevated Maze test) were tested. The antioxidant status in the cerebral cortex and the striatum were biochemically analyzed. Cd induces anxiety, and neuromotor, and thermal sensitivity deficits. EWH consumption prevented anxiety, neuromotor deficits, and alterations in thermal sensitivity, avoiding neuromotor deficits both when the administration was performed before or during Cd exposure. Both modes of administration reduced the levels of reactive species, and the lipid peroxidation increased by Cd and improved the striatum's antioxidant capacity. Pretreatment proved to be beneficial in preventing the reduction of SOD activity in the cortex. EWH could be used as a functional food with antioxidant properties capable of preventing neurological damage induced by Cd.
Assuntos
Cádmio , Clara de Ovo , Estresse Oxidativo , Ratos Wistar , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Cádmio/toxicidade , Clara de Ovo/química , Ratos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/prevenção & controle , Doenças do Sistema Nervoso/tratamento farmacológico , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologiaRESUMO
Aluminum (Al) is a non-essential metal omnipresent in human life and is considered an environmental toxicant. Al increases reactive oxygen production and triggers immune responses, contributing to chronic systemic inflammation development. Here, we have tested whether an egg white hydrolysate (EWH) with potential bioactive properties can protect against changes in reproductive function in rats exposed to long-term Al dietary levels at high and low doses. Male Wistar rats received orally: low aluminum level group-AlCl3 at 8.3 mg/kg b.w. for 60 days with or without EWH (1 g/kg/day); high aluminum level group-AlCl3 at 100 mg/kg b.w. for 42 days with or without EWH (1 g/kg/day). The co-administration of EWH prevented the increased Al deposition surrounding the germinative cells, reducing inflammation and oxidative stress in the reproductive organs. Furthermore, the daily supplementation with EWH maintained sperm production and sperm quality similar to those found in control animals, even after Al exposure at a high dietary contamination level. Altogether, our results suggest that EWH could be used as a protective agent against impairment in the reproductive system produced after long-term exposure to Al at low or high human dietary levels.
RESUMO
Aim: We investigated the antioxidant protective power of egg white hydrolysate (EWH) against the vascular damage induced by mercury chloride (HgCl2) exposure in resistance arteries. Methods: Male Wistar rats received for 60 days: (I) intramuscular injections (i.m.) of saline and tap water by gavage - Untreated group; (II) 4.6 µg/kg of HgCl2 i.m. for the first dose and subsequent doses of 0.07 µg/kg/day and tap water by gavage - HgCl2 group; (III) saline i.m. and 1 g/kg/day of EWH by gavage - EWH group, or (IV) the combination of the HgCl2 i.m. and EWH by gavage - EWH + HgCl2 group. Blood pressure (BP) was indirectly measured and dose-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), and noradrenaline (NE) were assessed in mesenteric resistance arteries (MRA), as in situ production of superoxide anion, nitric oxide (NO) release, vascular reactive oxygen species (ROS), lipid peroxidation, and antioxidant status. Results: Egg white hydrolysate prevented the elevation in BP and the vascular dysfunction after HgCl2 exposure; restored the NO-mediated endothelial modulation and inhibited the oxidative stress and inflammatory pathways induced by HgCl2. Conclusion: Egg white hydrolysate seems to be a useful functional food to prevent HgCl2-induced vascular toxic effects in MRA.
RESUMO
Exposure to high concentrations of cadmium (Cd), widely used in many industries and found in air, food and contaminated water, is not uncommon. Cd damages the cardiovascular system, but the vascular mechanisms involved are not fully understood. This study investigated the mechanisms involved in cardiovascular damage after exposure to high Cd concentrations. Three-month-old male Wistar rats were treated intraperitoneally for 14 days with distilled water (Untreated group) or 1â¯mg/kg cadmium chloride (Cd group). We investigated the systolic blood pressure (SBP) and vascular reactivity of mesenteric resistance arteries (MRA) and the aorta by analysing contractile and relaxation responses in the absence and presence of the endothelium; we also evaluated pathways involved in vascular tone regulation. Superoxide anion production, COX-2 protein expression and in situ detection of COX-2, AT-1, and NOX-1 were evaluated. Oxidative status, creatinine level and angiotensin-converting enzyme (ACE) activity in plasma were also evaluated. Fourteen-day exposure to a high Cd concentration induced hypertension associated with vascular dysfunction in MRA and the aorta. In both vessels, there was increased participation of cyclooxygenase 2 (COX2), angiotensin II type 1 (AT1) receptor and NOX1. MRA also presented endothelial dysfunction, denoted by impaired acetylcholine-mediated relaxation. All vascular changes were accompanied by increased reactive oxygen species production and COX2, NOX1 and AT1 receptor expression in vascular tissue. Overall, high Cd concentrations induced cardiovascular damage: hypertension, endothelial dysfunction and vascular damage in conductance and resistance arteries, NADPH oxidase, renin-angiotensin system and COX2 pathway activation.
Assuntos
Cloreto de Cádmio/toxicidade , Ciclo-Oxigenase 2/metabolismo , Endotélio Vascular/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Hipertensão/induzido quimicamente , NADPH Oxidases/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Pressão Sanguínea/efeitos dos fármacos , Cloreto de Cádmio/sangue , Relação Dose-Resposta a Droga , Endotélio Vascular/enzimologia , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Poluentes Ambientais/sangue , Hipertensão/enzimologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Injeções Intraperitoneais , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais , Vasoconstrição/efeitos dos fármacosRESUMO
Aluminum (Al) is toxic for humans and animals. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against cardiovascular changes in rats exposed to both high and low dietary levels of Al. Indeed, EWH has been previously shown to improve cardio metabolic dysfunctions induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3â¯mg/kg b.w. during 60 days) with or without EWH treatment (1â¯g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100â¯mg/kg b.w. during 42 days) with or without EWH treatment. After Al treatment, rats co-treated with EWH did not show vascular dysfunction or increased blood pressure as was observed in non EWH-cotreated animals. Indeed, co-treatment with EWH prevented the following effects observed in both aorta and mesenteric arteries: the increased vascular responses to phenylephrine (Phe), the decreased ACh-induced relaxation, the reduction on endothelial modulation of vasoconstrictor responses and the nitric oxide bioavailability, as well as the increased reactive oxygen species production from NAD(P)H oxidase. Altogether, our results suggest that EWH could be used as a protective agent against the harmful vascular effects after long term exposure to Al.
Assuntos
Antioxidantes/farmacologia , Proteínas do Ovo/farmacologia , Clara de Ovo/química , Hidrolisados de Proteína/farmacologia , Doenças Vasculares/prevenção & controle , Alumínio , Animais , Antioxidantes/química , Ciclo-Oxigenase 2/metabolismo , Proteínas do Ovo/química , Endotélio Vascular/efeitos dos fármacos , Hidrólise , Masculino , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Tromboxano-A Sintase/metabolismo , Doenças Vasculares/induzido quimicamente , Vasoconstrição/efeitos dos fármacosRESUMO
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.
Assuntos
Alumínio/toxicidade , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Clara de Ovo , Alimento Funcional , Hidrolisados de Proteína/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Comportamento Animal , Peso Corporal , Ciclo-Oxigenase 2/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
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 and at a high level exposure to Al on the peripheral nervous system. Wistar male rats were divided into two major groups and received orally: 1) First group - Low level - rats were subdivided and treated for 60days: a) Control - received ultrapure water; b) AlCl3 - received Al at 8.3mg/kg body weight (bw) for 60days; and 2) Second group - High level - rats were subdivided and treated for 42days: C) Control - received ultrapure water through oral gavage; d) AlCl3 - received Al at 100mg/kg bw for 42days. Von Frey hair test, plantar test, the presence of catalepsy and the spontaneous motor activity were investigated. Reactive oxygen species, lipid peroxidation and total antioxidant capacity, 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, increased inflammation in the sciatic nerve, systemic oxidative stress and, is able to be retained in the sciatic nerve. The effects of low-dose Al were similar to those found in rats exposed to Al at a dose much higher (100mg/kg). Our findings suggest that Al may be considered toxic for the peripheral nervous system, thus inducing peripheral dysfunction.
Assuntos
Alumínio/toxicidade , Neurite (Inflamação)/etiologia , Síndromes Neurotóxicas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/etiologia , Sistema Nervoso Periférico/efeitos dos fármacos , Poluentes da Água/toxicidade , Alumínio/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Catalepsia/etiologia , Relação Dose-Resposta a Droga , Hiperalgesia/etiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/metabolismo , Neurite (Inflamação)/fisiopatologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Ratos Wistar , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/imunologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Fatores de Tempo , Distribuição Tecidual , Testes de Toxicidade Crônica , Toxicocinética , Poluentes da Água/administração & dosagemRESUMO
ABSTRACT Objective: To determine whether different levels of CPAP improve the lung volumes and capacities of healthy subjects immersed in water. Methods: This was a randomized clinical trial, conducted between April and June of 2016, involving healthy female volunteers who were using oral contraceptives. Three 20-min immersion protocols were applied: control (no CPAP); CPAP5 (CPAP at 5 cmH2O); and CPAP10 (CPAP at 10 cmH2O). We evaluated HR, SpO2, FVC, FEV1, the FEV1/FVC ratio, peak expiratory flow rate (PEFR), and FEF25-75%) at three time points: pre-immersion; 10 min after immersion; and 10 min after the end of each protocol. Results: We evaluated 13 healthy volunteers. The CPAP10 protocol reversed the restrictive pattern of lung function induced by immersion in water, maintaining pulmonary volumes and capacities for a longer period than did the CPAP5 protocol. Conclusions: When the hemodynamic change causing a persistent lung disorder, only the application of higher positive pressures is effective in maintaining long-term improvements in the pulmonary profile.
RESUMO Objetivo: Verificar se continuous positive airway pressure (CPAP, pressão positiva contínua nas vias aéreas) em diferentes pressões melhora os volumes e capacidades pulmonares de sujeitos saudáveis em imersão em água. Métodos: Estudo clínico randomizado realizado entre abril e junho de 2016 com voluntárias saudáveis em uso de anticoncepcional oral. Foram aplicados três protocolos em imersão em água, todos com duração de 20 min: controle (sem aplicação de CPAP); CPAP5 (CPAP de 5 cmH2O); e CPAP10 (CPAP de 10 cmH2O). Avaliaram-se FC, SpO2, CVF, VEF1, relação VEF1/CVF em % do previsto, taxa de pico de fluxo expiratório e FEF25-75% em três momentos distintos: pré-imersão, 10 min após a imersão e 10 min após o final dos protocolos. Resultados: Foram avaliadas 13 voluntárias saudáveis. O protocolo CPAP10 foi capaz de reverter o padrão restritivo pulmonar induzido pela imersão em água em indivíduos saudáveis, mantendo normais os volumes e as capacidades pulmonares por um período mais prolongado quando comparado ao protocolo CPAP5. Conclusões: Nossos resultados indicam que, em condições cuja alteração hemodinâmica causadora do distúrbio pulmonar seja persistente, apenas a aplicação de pressões positivas mais elevadas é efetiva para manter as melhoras no quadro pulmonar por um maior tempo após a sua aplicação.
Assuntos
Humanos , Feminino , Adulto , Adulto Jovem , Pico do Fluxo Expiratório/fisiologia , Pressão Positiva Contínua nas Vias Aéreas , Imersão/fisiopatologia , Pulmão/fisiopatologia , Água , Índice de Massa Corporal , Modalidades de FisioterapiaRESUMO
The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl2, i.m., 1st dose 4.6µg/kg, subsequent doses 0.07µg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolysate-Mercury. Systolic (SBP) and diastolic (DBP) blood pressure measurement and vascular reactivity experiments in aorta were performed. We analyzed endothelial dependent and independent vasodilator responses and vasoconstrictor response to phenylephrine (Phe) in absence and presence of endothelium, a NOS inhibitor, a NADPH oxidase inhibitor, the superoxide dismutase, a non-selective COX inhibitor, a selective COX-2 inhibitor, an AT-1 receptors blocker. In situ superoxide anion production, SOD-1, NOX-4, p22phox, COX-2 and AT-1 mRNA levels and NOX-1 protein expression were performed in aorta while the determination of angiotensin converting enzyme (ACE) activity was measured in plasma. As results, EWH prevented the increase in SBP and Phe responses and the endothelial dysfunction elicited by Hg, which was related to decreased ACE activity and NOX activation by EWH and, subsequently, alleviated ROS production and improved NO bioavailability in aorta. In conclusion, EWH could be considered as alternative or complementary treatment tools for Hg-induced cardiovascular damage.
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Clara de Ovo/química , Mercúrio/toxicidade , NADPH Oxidases/sangue , Peptídeos/farmacologia , Peptidil Dipeptidase A/sangue , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/induzido quimicamente , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Masculino , NADPH Oxidases/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/farmacologiaRESUMO
Aluminum (Al) is a non-essential metal and a significant environmental contaminant and is associated with a number of human diseases including cardiovascular disease. We investigated the effects of Al exposure at doses similar to human dietary levels on the cardiovascular system over a 60day period. Wistar male rats were divided into two major groups and received orally: 1) Low aluminum level - rats were subdivided and treated for 60days as follows: a) Untreated - ultrapure water; b) AlCl3 at a dose of 8.3mg/kg bw for 60days, representing human Al exposure by diet; and 2) High aluminum level - rats were subdivided and treated for 42days as follows: C) Untreated - ultrapure water; d) AlCl3 at 100mg/kg bw for 42days, representing a high level of human exposure to Al. Effects on systolic blood pressure (SBP) and vascular function of aortic and mesenteric resistance arteries (MRA) were studied. Endothelium and smooth muscle integrity were evaluated by concentration-response curves to acetylcholine (ACh) and sodium nitroprusside. Vasoconstrictor responses to phenylephrine (Phe) in the presence and absence of endothelium and in the presence of the NOS inhibitor L-NAME, the potassium channels blocker TEA, the NAD(P)H oxidase inhibitor apocynin, superoxide dismutase (SOD), the non-selective COX inhibitor indomethacin and the selective COX-2 inhibitor NS 398 were analyzed. Vascular reactive oxygen species (ROS), lipid peroxidation and total antioxidant capacity, were measured. The mRNA expressions of eNOS, NAD(P)H oxidase 1 and 2, SOD1, COX-2 and thromboxane A2 receptor (TXA-2 R) were also investigated. Al exposure at human dietary levels impaired the cardiovascular system and these effects were almost the same as Al exposure at much higher levels. Al increased SBP, decreased ACh-induced relaxation, increased response to Phe, decreased endothelial modulation of vasoconstrictor responses, the bioavailability of nitric oxide (NO), the involvement of potassium channels on vascular responses, as well as increased ROS production from NAD(P)H oxidase and contractile prostanoids mainly from COX-2 in both aorta and mesenteric arteries. Al exposure increased vascular ROS production and lipid peroxidation as well as altered the antioxidant status in aorta and MRA. Al decreased vascular eNOS and SOD1 mRNA levels and increased the NAD(P)H oxidase 1, COX-2 and TXA-2 R mRNA levels. Our results point to an excess of ROS mainly from NAD(P)H oxidase after Al exposure and the increased vascular prostanoids from COX-2 acting in concert to decrease NO bioavailability, thus inducing vascular dysfunction and increasing blood pressure. Therefore, 60-day chronic exposure to Al, which reflects common human dietary Al intake, appears to pose a risk for the cardiovascular system.
Assuntos
Compostos de Alumínio/toxicidade , Pressão Sanguínea/efeitos dos fármacos , Cloretos/toxicidade , Ciclo-Oxigenase 2/metabolismo , Dieta , Endotélio Vascular/efeitos dos fármacos , Hipertensão/induzido quimicamente , NADH NADPH Oxirredutases/metabolismo , Vasoconstrição/efeitos dos fármacos , Cloreto de Alumínio , Animais , Inibidores de Ciclo-Oxigenase 2/farmacologia , Relação Dose-Resposta a Droga , Endotélio Vascular/enzimologia , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/enzimologia , Hipertensão/genética , Hipertensão/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , NADH NADPH Oxirredutases/antagonistas & inibidores , NADH NADPH Oxirredutases/genética , NADPH Oxidase 1 , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Receptores de Tromboxano A2 e Prostaglandina H2/efeitos dos fármacos , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Fatores de TempoRESUMO
Concerns about environmental aluminum (Al) and reproductive health have been raised. We investigated the effects of Al exposure at a human relevant dietary level and a high level exposure to Al. Experiment 1 (Lower level) rats were treated orally for 60 days: a) controls - ultrapure water; b) aluminum at 1.5mg/kg bw/day and c) aluminum at 8.3mg/kg bw/day. Experiment 2 (High level) rats were treated for 42 days: a) controls - ultrapure water; b) aluminum at 100mg/kg bw/day. Al decreased sperm count, daily sperm production, sperm motility, normal morphological sperm, impaired testis histology; increased oxidative stress in reproductive organs and inflammation in testis. Our study shows the specific presence of Al in the germinative cells and, that low concentrations of Al in testes (3.35µg/g) are sufficient to impair spermatogenesis and sperm quality. Our findings provide a better understanding of the reproductive health risk of Al.
Assuntos
Alumínio/toxicidade , Espermatozoides/efeitos dos fármacos , Animais , Dieta , Epididimo/efeitos dos fármacos , Epididimo/patologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/anormalidades , Espermatozoides/fisiologia , Testículo/efeitos dos fármacos , Testículo/patologiaRESUMO
AIMS: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl3) on blood pressure, vascular reactivity and oxidative stress. METHODS AND RESULTS: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl3: single dose of AlCl3 (100mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor l-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl3 exposure serum Al levels attained 147.7±25.0µg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. CONCLUSION: AlCl3-acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K+ channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular system.
Assuntos
Alumínio/toxicidade , Artérias/efeitos dos fármacos , Resistência Vascular , Animais , Artérias/metabolismo , Artérias/fisiologia , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Este estudo se propôs a avaliar os índices preditivos de desmante da ventilação mecânica: pressão inspiratória máxima, relação frequência respiratória/volume corrente (índice de Tobin) e teste em ventilação espontânea com tubo em T (teste TT). Foram estudados prospectivamente 34 pacientes sob ventilação mecânica por mais 24 horas com indicações de desmame. Pôde-se constatar, que os índices preditivos avaliados não foram diferentes entre pacientes que permaneceram ventilando espontaneamente e aqueles que apresentaram falência no desmame da ventilação mecânica