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1.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004527

RESUMO

The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung. Four kinases (PERK, PKR, GCN2 and HRI) sense a diverse range of stresses to trigger this "integrated stress response". Here we review recent advances identifying the integrated stress response as a critical pathway in the pathogenesis of pulmonary diseases, including pneumonias, thoracic malignancy, pulmonary fibrosis and pulmonary hypertension. Understanding the integrated stress response provides novel targets for the development of therapies.


Assuntos
Inflamação/metabolismo , Pneumopatias/metabolismo , Estresse Oxidativo/fisiologia , Biomarcadores/metabolismo , Humanos
2.
Medicine (Baltimore) ; 99(38): e21960, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957313

RESUMO

INTRODUCTION: Sperm DNA integrity has been considered as one of the important determinants of normal fertilization and embryonic development in natural and assisted pregnancy. It is difficult for men with high levels of sperm DNA fragmentation (SDF) in semen to conceive their partners naturally and assist in conception. The studies have found that the level of SDF in the semen of patients with varicocele (VC) was on the high side. In recent years, the effect of VC surgery on DNA fragmentation index has attracted the attention of researchers. In this study, we will evaluate the effectiveness of VC repair as a way to alleviate SDF and improve male fertility. METHODS AND ANALYSIS: Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of VC patients will be included. The potential outcome will include improvement in SDF, oxidative stress markers (reactive oxygen species, nitric oxide, and lipid peroxidation products), sperm chromatin compaction, other advanced sperm function characteristics, follow-up of fertility results. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on April 5th of 2021. CONCLUSION: This systematic review will provide more evidence to assess whether varicocelectomy is an effective intervention for patients with SDF. The results will be published in a public issue journal and offer the urologists help to make clinical decisions. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published research. Since this research does not involve patients, personal privacy will not be affected. The results of this review will be distributed to peer-reviewed journals or submitted to relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY202070119.


Assuntos
Fragmentação do DNA , Espermatozoides/patologia , Varicocele/cirurgia , Cromatina/metabolismo , Humanos , Masculino , Estresse Oxidativo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
3.
Free Radic Res ; 54(7): 525-534, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32873097

RESUMO

Slc7a11 (xCT) and Slc3a1 (rBAT) are cystine uptake transporters that maintain intracellular concentrations of cysteine, the rate-limiting amino acid in glutathione synthesis. This study was conducted to first determine the tissue distribution of the two transporters in male and female mice. Because Slc3a1 was the primary cystine transporter in liver, its sex-divergent expression, ontogeny, diurnal rhythm and whether its mRNA expression is altered by transcription factors (AhR, CAR, PXR, PPARα, and Nrf2) was also investigated. Slc7a11 was expressed highest in brain and gonads. Slc3a1 was expressed highest in kidney and intestine, followed by liver. Duodenal and hepatic Slc3a1 was higher in females than males. Hepatic Slc3a1 was high during darkness and low during daytime. Hepatic Scl3a1 was lowest pre-birth, increased to near maximal levels at birth, decreased back to pre-birth levels between Days 3-10, and then returned to peak levels by Day 45. Except for CAR, activation of transcription factors did not increase hepatic mRNA expression of Slc3a1. Chemical activation of CAR significantly induced Slc3a1 1.4-fold in wild-type but not CAR-null mice. Slc3a1 mRNA was higher in livers of AhR- and Nrf2-null mice compared to wild-type mice. High doses of diquat but not acetaminophen induced Slc3a1, suggesting Slc3a1 may respond to oxidative stress but not necessarily to GSH depletion. Overall, Slc7a11 is mainly expressed in brain and gonads, whereas Slc3a1 is mainly expressed in kidney, small intestine and liver, and its hepatic expression is regulated by diurnal rhythm and certain xenobiotic treatments.


Assuntos
Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Cistina/metabolismo , Sistemas de Transporte de Aminoácidos Básicos/biossíntese , Sistemas de Transporte de Aminoácidos Básicos/genética , Sistemas de Transporte de Aminoácidos Neutros/biossíntese , Sistemas de Transporte de Aminoácidos Neutros/genética , Animais , Feminino , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Tecidual
4.
Medicine (Baltimore) ; 99(31): e21492, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756181

RESUMO

Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Insuficiência Renal Crônica/sangue , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Renina-Angiotensina/fisiologia
5.
Medicina (Kaunas) ; 56(8)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752010

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the corona virus disease-19 which is accompanied by severe pneumonia, pulmonary alveolar collapses and which stops oxygen exchange. Viral transmissibility and pathogenesis depend on recognition by a receptor in the host, protease cleavage of the host membrane and fusion. SARS-CoV-2 binds to the angiotensin converting enzyme 2 receptor. Here, we discuss the general characteristics of the virus, its mechanism of action and the way in which the mechanism correlates with the comorbidities that increase the death rate. We also discuss the currently proposed therapeutic measures and propose the use of antioxidant drugs to help patients infected with the SARS-CoV-2. Oxidizing agents come from phagocytic leukocytes such as neutrophils, monocytes, macrophages and eosinophils that invade tissue. Free radicals promote cytotoxicity thus injuring cells. They also trigger the mechanism of inflammation by mediating the activation of NFkB and inducing the transcription of cytokine production genes. Release of cytokines enhances the inflammatory response. Oxidative stress is elevated during critical illnesses and contributes to organ failure. In corona virus disease-19 there is an intense inflammatory response known as a cytokine storm that could be mediated by oxidative stress. Although antioxidant therapy has not been tested in corona virus disease-19, the consequences of antioxidant therapy in sepsis, acute respiratory distress syndrome and acute lung injury are known. It improves oxygenation rates, glutathione levels and strengthens the immune response. It reduces mechanical ventilation time, the length of stay in the intensive care unit, multiple organ dysfunctions and the length of stay in the hospital and mortality rates in acute lung injury/acute respiratory distress syndrome and could thus help patients with corona virus disease-19.


Assuntos
Antioxidantes/farmacologia , Betacoronavirus/fisiologia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia
6.
Food Chem Toxicol ; 145: 111701, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858131

RESUMO

Obesity and its related metabolic disorders, as well as infectious diseases like covid-19, are important health risks nowadays. It was recently documented that long-term fasting improves metabolic health and enhanced the total antioxidant capacity. The present study investigated the influence of a 10-day fasting on markers of the redox status in 109 subjects. Reducing power, 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation(ABTS) radical scavenging capacity, and hydroxyl radical scavenging capacity increased significantly, and indicated an increase of circulating antioxidant levels. No differences were detected in superoxide scavenging capacity, protein carbonyls, and superoxide dismutase when measured at baseline and after 10 days of fasting. These findings were concomitant to a decrease in blood glucose, insulin, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) and triglycerides as well as an increase in total cholesterol/high-density lipoprotein (HDL) ratio. In addition, the well-being index as well as the subjective energy levels increased, documenting a good tolerability. There was an interplay between redox and metabolic parameters since lipid peroxidation baseline levels (thiobarbituric acid reactive substances [TBARS]) affected the ability of long-term fasting to normalize lipid levels. A machine learning model showed that a combination of antioxidant parameters measured at baseline predicted the efficiency of the fasting regimen to decrease LDL levels. In conclusion, it was demonstrated that long-term fasting enhanced the endogenous production of antioxidant molecules, that act protectively against free radicals, and in parallel improved the metabolic health status. Our results suggest that the outcome of long-term fasting strategies could be depending on the baseline values of the antioxidative and metabolic status of subjects.


Assuntos
Jejum/metabolismo , Depuradores de Radicais Livres/metabolismo , Obesidade/dietoterapia , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Peroxidação de Lipídeos/fisiologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto Jovem
7.
Khirurgiia (Mosk) ; (7): 12-17, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736458

RESUMO

OBJECTIVE: To determine the value of membrane protective effect in intestine and liver cells for the effectiveness of minimally invasive surgery for acute peritonitis. MATERIAL AND METHODS: Patients with acute peritonitis undergoing laparoscopic (n=60) and open (n=50) surgery are analyzed. Functional characteristics of liver and bowel, disorders of homeostasis were evaluated in early postoperative period. RESULTS: Reduced negative impact of surgical aggression on the state of liver and intestine is essential to improve treatment outcomes in patients with acute peritonitis undergoing minimally invasive surgery. Fast recovery of intestine inevitably results reduced release of endotoxins while restoration of liver function is associated with rapid elimination of these toxins. These processes prevent severe intoxication and facilitate accelerated recovery. Functional restoration of liver and bowel is associated with reduced oxidative stress during laparoscopic operations. It is also important because peritonitis causes activation of free-radical processes per se. Therefore, an additional source of oxidative phenomena is extremely undesirable in these cases. CONCLUSION: Laparoscopic surgery for acute peritonitis minimizes surgical aggression and is associated with more favorable recovery of liver and bowel function. Undoubtedly, these findings should be considered to choose surgical approach in this severe category of patients.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Peritonite/cirurgia , Doença Aguda , Membrana Celular/metabolismo , Membrana Celular/patologia , Membrana Celular/fisiologia , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Intestinos/fisiopatologia , Laparoscopia/efeitos adversos , Laparotomia/efeitos adversos , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Estresse Oxidativo/fisiologia , Peritonite/metabolismo , Peritonite/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica , Toxinas Biológicas/biossíntese , Toxinas Biológicas/metabolismo
8.
PLoS One ; 15(8): e0231514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785261

RESUMO

Iron Overload Disorder (IOD) is a syndrome developed by captive browsing rhinoceroses like black rhinoceroses (Diceros bicornis), in which hemosiderosis develops in vital organs while free iron accumulates in the body, potentially predisposing to various secondary diseases. Captive grazing species like white rhinoceroses (Ceratotherium simum) do not seem to be affected. The authors hypothesized that inflammation and oxidative stress may be implicated in the pathogenesis of IOD in captive black rhinoceroses, making this syndrome a potential common denominator to various diseases described in captivity in this species. In this prospective study, 15 black (BR) and 29 white rhinoceroses (WR) originating from 22 European zoos were blood-sampled and compared for their iron status (serum iron), liver/muscle biochemical parameters (AST, GGT, cholesterol), inflammatory status (total proteins, protein electrophoresis) and oxidative stress markers (SOD, GPX, dROMs). Results showed higher serum iron and liver enzyme levels in black rhinoceroses (P < 0.01), as well as higher dROMs (P < 0.01) and a trend for higher GPX (P = 0.06) levels. The albumin/globulin ratio was lower in black rhinoceroses (P < 0.05) due to higher α2-globulin levels (P < 0.001). The present study suggests a higher inflammatory and oxidative profile in captive BR than in WR, possibly in relation to iron status. This could be either a consequence or a cause of iron accumulation. Further investigations are needed to assess the prognostic value of the inflammatory and oxidative markers in captive black rhinoceroses, particularly for evaluating the impact of reduced-iron and antioxidant-supplemented diets.


Assuntos
Sobrecarga de Ferro/imunologia , Sobrecarga de Ferro/metabolismo , Perissodáctilos/metabolismo , Animais , Animais de Zoológico/metabolismo , Suscetibilidade a Doenças/metabolismo , Feminino , Inflamação/metabolismo , Ferro/metabolismo , Fígado/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Estudos Prospectivos
9.
PLoS Pathog ; 16(7): e1008645, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667960

RESUMO

Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.


Assuntos
Aspergilose , Aspergillus fumigatus/patogenicidade , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/fisiologia , Gliotoxina/biossíntese , Fatores de Transcrição/metabolismo , Animais , Aspergilose/metabolismo , Aspergilose/microbiologia , Aspergillus fumigatus/metabolismo , Camundongos , Estresse Oxidativo/fisiologia , Virulência/fisiologia
10.
Molecules ; 25(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707945

RESUMO

Vitamin B3, or niacin, is one of the most important compounds of the B-vitamin complex. Recent reports have demonstrated the involvement of vitamin B3 in a number of pivotal functions which ensure that homeostasis is maintained. In addition, the intriguing nature of its synthesis and the underlying mechanism of action of vitamin B3 have encouraged further studies aimed at deepening our understanding of the close link between the exogenous supply of B3 and how it activates dependent enzymes. This crucial role can be attributed to the gut microflora and its ability to shape human behavior and development by mediating the bioavailability of metabolites. Recent studies have indicated a possible interconnection between the novel coronavirus and commensal bacteria. As such, we have attempted to explain how the gastrointestinal deficiencies displayed by SARS-CoV-2-infected patients arise. It seems that the stimulation of a proinflammatory cascade and the production of large amounts of reactive oxygen species culminates in the subsequent loss of host eubiosis. Studies of the relationhip between ROS, SARS-CoV-2, and gut flora are sparse in the current literature. As an integrated component, oxidative stress (OS) has been found to negatively influence host eubiosis, in vitro fertilization outcomes, and oocyte quality, but to act as a sentinel against infections. In conclusion, research suggests that in the future, a healthy diet may be considered a reliable tool for maintaining and optimizing our key internal parameters.


Assuntos
Infecções por Coronavirus/patologia , Microbioma Gastrointestinal/fisiologia , Niacina/metabolismo , Niacinamida/metabolismo , Estresse Oxidativo/fisiologia , Pneumonia Viral/patologia , Betacoronavirus/metabolismo , Disbiose/fisiopatologia , Humanos , Pandemias , Espécies Reativas de Oxigênio/metabolismo
11.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R264-R281, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609539

RESUMO

Long-term exposure of Mytilus galloprovincialis to temperatures beyond 26°C triggers mussel mortality. The present study aimed to integratively illustrate the correlation between intermediary metabolism, hsp gene expression, and oxidative stress-related proteins in long-term thermally stressed Mytilus galloprovincialis and whether they are affected by thermal stress magnitude and duration. We accordingly evaluated the gene expression profiles, in the posterior adductor muscle (PAM) and the mantle, concerning heat shock protein 70 and 90 (hsp70 and hsp90), and the antioxidant defense indicators Mn-SOD, Cu/Zn-SOD, catalase, glutathione S-transferase, and the metallothioneins mt-10 and mt-20. Moreover, we determined antioxidant enzyme activities, oxidative stress through lipid peroxidation, and activities of intermediary metabolism enzymes. The pattern of changes in relative mRNA expression levels indicate that mussels are able to sense thermal stress even when exposed to 22°C and before mussel mortality is initiated. Data indicate a close correlation between the magnitude and duration of thermal stress with lipid peroxidation levels and changes in the activity of antioxidant enzymes and the enzymes of intermediary metabolism. The gene expression and increase in the activities of antioxidant enzymes support a scenario, according to which exposure to 24°C might trigger reactive oxygen species (ROS) production, which is closely correlated with anaerobic metabolism under hypometabolic conditions. Increase and maintenance of oxidative stress in conjunction with energy balance disturbance seem to trigger mussel mortality after long-term exposure at temperatures beyond 26°C. Eventually, in the context of preparation for oxidative stress, certain hypotheses and models are suggested, integrating the several steps of cellular stress response.


Assuntos
Proteínas de Choque Térmico/metabolismo , Mytilus/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Antioxidantes/metabolismo , Expressão Gênica/fisiologia , Peroxidação de Lipídeos/fisiologia , Camundongos , Estresse Fisiológico/fisiologia
12.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R203-R210, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609535

RESUMO

Canids are a morphological and physiological diverse group of animals, with the most diversity found within one species, the domestic dog. Underlying observed morphological differences, there must also be differences at other levels of organization that could lead to elucidating aging rates and life span disparities between wild and domestic canids. Furthermore, small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated, although oxidative stress has been implicated as a potential culprit of the disparate life spans of domestic dogs. We used plasma and red blood cells from known aged domestic dogs and wild canids, and measured several oxidative stress variables: total antioxidant capacity (TAC), lipid damage, and enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase (GPx). We used phylogenetically informed general linear mixed models and nonphylogenetically corrected linear regression analysis. We found that lipid damage increases with age in domestic dogs, whereas TAC increases with age and TAC and GPx activity increases as a function of age/maximum life span in wild canids, which may partly explain longer potential life spans in wolves. As body mass increases, TAC and GPx activity increase in wild canids, but not domestic dogs, highlighting that artificial selection may have decreased antioxidant capacity in domestic dogs. We found that small-breed dogs have significantly higher circulating lipid damage compared with large-breed dogs, concomitant to their high mass-specific metabolism and higher growth rates, but in opposition to their long life spans.


Assuntos
Peso Corporal/fisiologia , Longevidade/fisiologia , Estresse Oxidativo/fisiologia , Animais , Canidae , Catalase/sangue , Cães , Feminino , Glutationa Peroxidase/sangue , Masculino , Oxirredução , Filogenia , Superóxido Dismutase/sangue
13.
Artigo em Inglês | MEDLINE | ID: mdl-32645886

RESUMO

The aim of this study was to analyze the changes in biochemical markers of oxidative stress and muscle damage, as well as psychomotor abilities during a military survival training. The study included 15 soldiers of special unit (SU), that completed 48 h military survival training combined with sleep deprivation. Before the training (P1), after 24 h (P2), and after 48 h of training (P3), blood samples were taken to measure biochemical markers. At the same time points, the measurements of divided attention and handgrip strength were conducted. Glutathione peroxidase activity decreased significantly at P3, in comparison with P1 and P2 (p < 0.0001), however, no changes were observed in other biochemical markers (i.e., lipid hydroperoxides, creatine kinase and superoxide dismutase activity) throughout the survival training (p > 0.05). The divided attention index was improved significantly at P2 and P3, as compared to P1 (p < 0.05). A tendency to change in maximum strength was found during the training period (main time effect; p = 0.08). Moreover, the strength differentiation (i.e., 50% maximum strength; 50%max) was higher at P3 than at P1 and P2 (p < 0.05). In conclusion, the 48 h survival training in the SU soldiers does not cause oxidative stress or muscle tissue damage, as well as any deterioration, and even improvement in psychomotor abilities. However, the change in strength differentiation (i.e., the production above 60%max instead of target 50%max) after the training may point to deterioration in motor control. Although it should be confirmed in further study with a more numerous group of soldiers, our findings indicate that the special unit soldiers will be able to perform, in a correct manner, specialized tasks related to their long-term activities, especially those which require divided attention. However, participation in long-term survival training, even with low workload, combined with sleep deprivation, results in a deterioration in motor control which may indicate the relevance of monitoring coordination motor abilities/skills in the training process of special unit soldiers.


Assuntos
Exercício Físico/fisiologia , Militares , Destreza Motora , Estresse Oxidativo/fisiologia , Privação do Sono , Sobrevida/fisiologia , Biomarcadores/sangue , Força da Mão/fisiologia , Humanos , Resistência Física/fisiologia
14.
PLoS One ; 15(7): e0236357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687509

RESUMO

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50µg iv+arginine 0,5 g/Kg test, with a peak GH response <9 µg /L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.


Assuntos
Antioxidantes/análise , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/metabolismo , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina/urina , Adulto , Malformação de Arnold-Chiari/sangue , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Síndrome da Sela Vazia/sangue , Síndrome da Sela Vazia/complicações , Síndrome da Sela Vazia/metabolismo , Feminino , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/etiologia , Hipopituitarismo/urina , Peroxidação de Lipídeos , Lisina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Síndrome Metabólica/urina , Pessoa de Meia-Idade , Triptofano/análogos & derivados , Triptofano/sangue , Tirosina/análogos & derivados , Tirosina/urina
15.
Mol Immunol ; 125: 24-31, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32623292

RESUMO

Toll-like receptor 9 (TLR9) has been reported to mediate airway inflammation, however, the underlying mechanism is poorly understood. In the present study, our objective was to reveal whether TLR9 regulates NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation and Raw264.7 cells. Female wild type(WT)and TLR9-/-mice on C57BL/6 background were used to induce allergic airway inflammation by challenge of OVA, and Raw264.7 cells with or without TLR9 knockdown by small interfering RNA (siRNA) were stimulated by S.aureus. The results demonstrated that deletion of TLR9 effectively attenuated OVA-induced allergic airway inflammation including inflammatory cells infiltration and goblet cell hyperplasia. Meanwhile, OVA-induced protein expression of NLRP3, caspase-1(p20) and mature IL-1ß, as well as secretion of IL-1ß and IL-18 in wild type mice (WT) was obviously suppressed by TLR9 deficiency. Concomitantly, the expression of oxidative markers 8-OhDG and nitrotyrosine was increased in OVA-challenged WT mice, while TLR9 deficiency significantly inhibited such increase. Similarly, in the in vitro study, we found that knockdown of TLR9 markedly suppressed S.aureus-induced activation of NLRP3 inflammasome and oxidative stress in Raw264.7 cells. Collectively, our findings indicated that TLR9 may mediate allergic airway inflammation via activating NLRP3 inflammasome and oxidative stress.


Assuntos
Asma/imunologia , Hipersensibilidade/imunologia , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Estresse Oxidativo/fisiologia , Receptor Toll-Like 9/imunologia , Animais , Asma/metabolismo , Hipersensibilidade/metabolismo , Hipersensibilidade/fisiopatologia , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/fisiopatologia , Células RAW 264.7 , Receptor Toll-Like 9/metabolismo
16.
Ecotoxicol Environ Saf ; 202: 110889, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32623235

RESUMO

Coke oven emissions (COEs) can cause oxidative stress of the body, which in turn induces the occupational lung disease and also increases the risk of other diseases. COEs are the major occupational hazard factors for coke oven workers. The aim of the study is to explore the influences of COEs exposure on oxidative damage and estimate the benchmark dose (BMD) of COEs. A group of 542 workers exposed to COEs and 237 healthy controls from the same city were recruited in this study. The corresponding measuring kits were used to determine the plasma biomarkers of oxidative damage level. Generalized linear models and trend tests were used to analyze the relationship between COEs exposure and biomarkers. EPA Benchmark Dose Software was performed to calculate BMD and the lower confidence limit of the benchmark dose (BMDL) of COEs exposure. A significant association was observed between COEs exposure and oxidative damage with T-AOC as a biomarker. The BMD of COEs exposure were 2.83 mg/m3 and 1.39 mg/m3 for males and females, respectively, and the corresponding BMDL were 1.47 mg/m3 and 0.75 mg/m3, respectively. Our results suggested that the exposure level of COEs below the current national occupational exposure limits (OELs) would induce oxidative damage, and the OEL of COEs based on the T-AOC damage was suggested at 0.03 mg/m3 in this study.


Assuntos
Coque/toxicidade , Doenças Profissionais/metabolismo , Exposição Ocupacional/análise , Estresse Oxidativo/fisiologia , Adulto , Grupo com Ancestrais do Continente Asiático , Benchmarking , Biomarcadores/metabolismo , Coque/análise , Dano ao DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Hidrocarbonetos Policíclicos Aromáticos/análise , Pirenos/análise , Resíduos
17.
Mem Inst Oswaldo Cruz ; 115: e190469, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638832

RESUMO

BACKGROUND Oxidative stress is responsible for generating DNA lesions and the 8-oxoguanine (8-oxoG) is the most commonly lesion found in DNA damage. When this base is incorporated during DNA replication, it could generate double-strand DNA breaks and cellular death. MutT enzyme hydrolyzes the 8-oxoG from the nucleotide pool, preventing its incorporation during DNA replication. OBJECTIVES To investigate the importance of 8-oxoG in Leishmania infantum and L. braziliensis, in this study we analysed the impact of heterologous expression of Escherichia coli MutT (EcMutT) enzyme in drug-resistance phenotype and defense against oxidative stress. METHODS Comparative analysis of L. braziliensis and L. infantum H2O2 tolerance and cell cycle profile were performed. Lines of L. braziliensis and L. infantum expressing EcMutT were generated and evaluated using susceptibility tests to H2O2 and SbIII, cell cycle analysis, γH2A western blotting, and BrdU native detection assay. FINDINGS Comparative analysis of tolerance to oxidative stress generated by H2O2 showed that L. infantum is more tolerant to exogenous H2O2 than L. braziliensis. In addition, cell cycle analysis showed that L. infantum, after treatment with H2O2, remains in G1 phase, returning to its normal growth rate after 72 h. In contrast, after treatment with H2O2, L. braziliensis parasites continue to move to the next stages of the cell cycle. Expression of the E. coli MutT gene in L. braziliensis and L. infantum does not interfere in parasite growth or in susceptibility to SbIII. Interestingly, we observed that L. braziliensis EcMutT-expressing clones were more tolerant to H2O2 treatment, presented lower activation of γH2A, a biomarker of genotoxic stress, and lower replication stress than its parental non-transfected parasites. In contrast, the EcMutT is not involved in protection against oxidative stress generated by H2O2 in L. infantum. MAIN CONCLUSIONS Our results showed that 8-oxoG clearance in L. braziliensis is important to avoid misincorporation during DNA replication after oxidative stress generated by H2O2.


Assuntos
Antimônio/toxicidade , Proteínas de Escherichia coli/genética , Escherichia coli , Guanina/análogos & derivados , Leishmania braziliensis/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Pirofosfatases , Superóxido Dismutase/metabolismo , Animais , Antiprotozoários/farmacologia , Proteínas de Escherichia coli/metabolismo , Guanina/farmacologia , Humanos , Peróxido de Hidrogênio/toxicidade , Leishmania braziliensis/enzimologia , Leishmania infantum/enzimologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pirofosfatases/genética , Pirofosfatases/metabolismo , Coelhos , Ratos , Superóxido Dismutase/genética
18.
Rev Assoc Med Bras (1992) ; 66(5): 600-606, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638970

RESUMO

OBJECTIVE Lower physical fitness and poor motor performance were shown to be linked with higher levels of oxidative stress in children and adolescents with intellectual disabilities. Therefore, a moderate aerobic exercise for 12-weeks was performed to evaluate the effects of physical activity scores on motor functions, oxidative stress, and intelligence quotients (IQ) in school children with intellectual disability. METHODS A total of 65 school children aged (12-18 Yrs) were randomly included in this study. Intellectual disability (ID),motor skills,physical fitness(VO2max), total energy expenditure (TEE), MDA, 8-OHdG, TAC, NO, and total oxidative stress(OS)were assessed using pre-validated WISC-IQ score test, BOT-2 test, PA questionnaire, and immunoassay techniques respectively. RESULTS WISC-IQ and BOT-2 set scores of intellectual and motor skills performance showed a significant correlation with physical activity status and the regulation of oxidative stress-free radicals in school children with mild and moderate ID following 12 weeks of moderate exercise. The intellectual and motor skills performance of the participants correlated positively with the increase in TAC activity and physical fitness scores and negatively with MDA, 8-OHdG, NO, and Total-OS, respectively. Stepwise multiple regression analysis of the demographic, physical status and oxidative stress parameters explained around78.0 to 93.4 % of intellectual disability variation among schoolchildren. CONCLUSION Moderate aerobic training for12 weeks has a positive impact on improving intellectual ability of schoolchildren with ID via modulating redox status, improves physical fitness, and motor skills proficiency.


Assuntos
Deficiência Intelectual , Aptidão Física , Adolescente , Biomarcadores/metabolismo , Criança , Exercício Físico , Humanos , Oxirredução , Estresse Oxidativo/fisiologia
19.
Toxicon ; 185: 203-212, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32687887

RESUMO

The mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide, frequently resulting in poor performance and economic losses. Data concerning the effects on poultry health or focusing on intestinal toxicity or the response to oxidative stress are scarce. Also, there is a need for strategies to mitigate the negative effects of DON. This study aimed to investigate the effects of Lactobacillus spp. treatments on the intestine, liver and kidney of poultry fed a DON-contaminated diet. To achieve this aim, histological, morphometrical and histochemical assays were performed. The oxidative stress response was also analyzed by the tests: reduced glutathione, ferric reducing ability, reducing of 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid), nitro blue tetrazolium detection of superoxide anion, and thiobarbituric acid reactive substances. One-day-old broilers chickens (n 50) were submitted to the following treatments: control, DON (19.3 mg kg-1), viable Lactobacillus spp. + DON (VL + DON), heat-inactivated Lactobacillus spp. + DON (HIL + DON), Lactobacillus spp. culture supernatant + DON (LCS + DON). The animals received the contaminated diet for seven days. DON increased the intestinal and liver lesion score, while the Lactobacillus spp. treatments (LT) remained like the control. DON reduced the villi height and increased the crypt depths. The LT showed crypt depths similar to control, and higher villi: crypt ratio in duodenum and jejunum. In the ileum, the LT reduced the goblet cell count in relation to DON group. DON increased the number of intraepithelial lymphocytes (IEL) in jejunum and ileum, while the VL + DON treatment induced a significant decrease in IEL in comparison to DON. DON-diet induced an oxidative stress response in the intestine and liver, and also reduced the antioxidant capacity in these tissues, while LT treatments remained mostly similar to control. DON induced no change in redox balance in the kidney. The LT improved the intestinal health after DON acute exposure, reducing the oxidative stress damage mainly on jejunum and liver.


Assuntos
Galinhas/microbiologia , Micotoxinas/toxicidade , Estresse Oxidativo/fisiologia , Tricotecenos/toxicidade , Ração Animal , Animais , Contaminação de Alimentos , Intestinos , Lactobacillus
20.
Life Sci ; 257: 118138, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712298

RESUMO

AIMS: Hypertension is a relevant sex and sex hormones-dependent risk factor where the cardiovascular and renal health of the population are concerned. Men experience greater losses of renal function (RF) than women, but the mechanisms remain somewhat unclear. Our goal was to evaluate the relationship between oxidative stress (OS), angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activities and RF in male and female SHR. MAIN METHODS: Twelve-week-old spontaneously hypertensive rats (SHR) were submitted to either castration or SHAM surgery and divided into 4 groups, SHAM or Castrated (CAST) males or females. After 51 days we evaluated RF (inulin and sodium para-aminohippurate), ACE and ACE2 activities (fluorimetry), OS (flow cytometry), collagen deposition (picrosirius red) and protein expression (western blot). KEY FINDINGS: Males presented lower RF than females and castration impaired this parameter in both groups. Sexual dimorphism was not observed regarding OS and inflammation; however, castration increased this parameter more severely in males than in females. SHAM males exhibited higher collagen deposition than females, though castration increased it in both sexes, eliminating the difference. We found sexual dimorphism regarding renal ACE and ACE2 activities, which were lower in males than in females. Although castration did not alter ACE activity, it reduced ACE2 activity in females and increased it in males. SIGNIFICANCE: These results indicate that sex hormones affect RF in SHR. As alterations in the oxidative system were capable of promoting podocyte injury, inflammation, and collagen deposition, we put forward that these effects are differently modulated by ACE and ACE2.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Nefropatias/etiologia , Estresse Oxidativo , Peptidil Dipeptidase A/metabolismo , Ratos Endogâmicos SHR/metabolismo , Animais , Western Blotting , Colágeno/metabolismo , Feminino , Rim/enzimologia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Orquiectomia , Ovariectomia , Estresse Oxidativo/fisiologia , Ratos , Ratos Endogâmicos SHR/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fatores Sexuais
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