Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.825
Filtrar
1.
Zool Res ; 42(5): 592-605, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34387415

RESUMO

The large yellow croaker (Larimichthys crocea), which is an economically important mariculture fish in China, is often exposed to environmental hypoxia. Reactive oxygen species (ROS) homeostasis is essential for the maintenance of normal physiological conditions in an organism. Direct evidence that environmental hypoxia leads to ROS overproduction is scarce in marine fish. Furthermore, the sources of ROS overproduction in marine fish under hypoxic stress are poorly known. In this study, we investigated the effects of hypoxia on redox homeostasis in L. crocea and the impact of impaired redox homeostasis on fish. We first confirmed that hypoxia drove ROS production mainly via the mitochondrial electron transport chain and NADPH oxidase complex pathways in L. crocea and its cell line (large yellow croaker fry (LYCF) cells). We subsequently detected a marked increase in the antioxidant systems of the fish. However, imbalance between the pro-oxidation and antioxidation systems ultimately led to excessive ROS and oxidative stress. Cell viability showed a remarkable decrease while oxidative indicators, such as malondialdehyde, protein carbonylation, and 8-hydroxy-2 deoxyguanosine, showed a significant increase after hypoxia, accompanied by tissue damage. N-acetylcysteine (NAC) reduced ROS levels, alleviated oxidative damage, and improved cell viability in vitro. Appropriate uptake of ROS scavengers (e.g., NAC and elamipretide Szeto-Schiller-31) and inhibitors (e.g., apocynin, diphenylene iodonium, and 5-hydroxydecanoate) may be effective at overcoming hypoxic toxicity. Our findings highlight previously unstudied strategies of hypoxic toxicity resistance in marine fish.


Assuntos
Antioxidantes/metabolismo , Peixes/metabolismo , Estresse Oxidativo/fisiologia , Oxigênio/química , Oxigênio/metabolismo , Espécies Reativas de Oxigênio , Animais , Linhagem Celular , Sobrevivência Celular , Meio Ambiente , Homeostase , NADP
2.
FASEB J ; 35(9): e21831, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34383982

RESUMO

The nuclear factor of activated T-cells 5 (NFAT5) is a transcriptional regulator of macrophage activation and T-cell development, which controls stabilizing responses of cells to hypertonic and biomechanical stress. In this study, we detected NFAT5 in the media layer of arteries adjacent to human arteriosclerotic plaques and analyzed its role in vascular smooth muscle cells (VSMCs) known to contribute to arteriosclerosis through the uptake of lipids and transformation into foam cells. Exposure of both human and mouse VSMCs to cholesterol stimulated the nuclear translocation of NFAT5 and increased the expression of the ATP-binding cassette transporter Abca1, required to regulate cholesterol efflux from cells. Loss of Nfat5 promoted cholesterol accumulation in these cells and inhibited the expression of genes involved in the management of oxidative stress or lipid handling, such as Sod1, Plin2, Fabp3, and Ppard. The functional relevance of these observations was subsequently investigated in mice fed a high-fat diet upon induction of a smooth muscle cell-specific genetic ablation of Nfat5 (Nfat5(SMC)-/- ). Under these conditions, Nfat5(SMC)-/- but not Nfat5fl/fl mice developed small, focal lipid-rich lesions in the aorta after 14 and 25 weeks, which were formed by intracellular lipid droplets deposited in the sub-intimal VSMCs layer. While known for being activated by external stimuli, NFAT5 was found to mediate the expression of VSMC genes associated with the handling of lipids in response to a cholesterol-rich environment. Failure of this protective function may promote the formation of lipid-laden arterial VSMCs and pro-atherogenic vascular responses.


Assuntos
Aorta/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fatores de Transcrição/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Idoso , Animais , Aterosclerose/metabolismo , Células Cultivadas , Colesterol/metabolismo , Feminino , Células Espumosas/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Hipercolesterolemia/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Túnica Íntima/metabolismo
3.
Nutrients ; 13(8)2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34444947

RESUMO

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Recently, also natural antioxidants have been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measurements at baseline and after completion of the three weeks PR. We found that daily vegetable intake in normal diet, without any specific intervention, can increase the probability to successfully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of non-responders, p = 0.033). The association was especially evident in subjects ≥ 80 year of age (OR = 17.0; p < 0.019). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an improvement in the patient's inflammatory state.


Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Fenômenos Fisiológicos da Nutrição do Idoso/fisiologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Verduras , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/administração & dosagem , Dano ao DNA/fisiologia , Inquéritos sobre Dietas , Feminino , Humanos , Inflamação , Pulmão/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento
4.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445113

RESUMO

Nuclear factor erythroid 2-related factor (Nrf2) is a transcriptional activator of the cell protection gene that binds to the antioxidant response element (ARE). Therefore, Nrf2 protects cells and tissues from oxidative stress. Normally, Kelch-like ECH-associated protein 1 (Keap1) inhibits the activation of Nrf2 by binding to Nrf2 and contributes to Nrf2 break down by ubiquitin proteasomes. In moderate oxidative stress, Keap1 is inhibited, allowing Nrf2 to be translocated to the nucleus, which acts as an antioxidant. However, under unusually severe oxidative stress, the Keap1-Nrf2 mechanism becomes disrupted and results in cell and tissue damage. Oxide-containing atmospheric environment generally contributes to the development of respiratory diseases, possibly leading to the failure of the Keap1-Nrf2 pathway. Until now, several studies have identified changes in Keap1-Nrf2 signaling in models of respiratory diseases, such as acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma. These studies have confirmed that several Nrf2 activators can alleviate symptoms of respiratory diseases. Thus, this review describes how the expression of Keap1-Nrf2 functions in different respiratory diseases and explains the protective effects of reversing this expression.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Doenças Respiratórias/metabolismo , Animais , Antioxidantes/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia
5.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445675

RESUMO

The term resilience, which has been present in science for almost half a century, stands for the capacity of some system needed to overcome an amount of disturbance from the environment in order to avoid a change to another stable state. In medicine, the concept of resilience means the ability to deal with daily stress and disturbance to our homeostasis with the intention of protecting it from disturbance. With aging, the organism becomes more sensitive to environmental impacts and more susceptible to changes. Mental disturbances and a decline in psychological resilience in older people are potentiated with many social and environmental factors along with a subjective perception of decreasing health. Distinct from findings in younger age groups, mental and physical medical conditions in older people are closely associated with each other, sharing common mechanisms and potentiating each other's development. Increased inflammation and oxidative stress have been recognized as the main driving mechanisms in the development of aging diseases. This paper aims to reveal, through a translational approach, physiological and molecular mechanisms of emotional distress and low psychological resilience in older individuals as driving mechanisms for the accelerated development of chronic aging diseases, and to systematize the available information sources on strategies for mitigation of low resilience in order to prevent chronic diseases.


Assuntos
Envelhecimento/fisiologia , Resiliência Psicológica , Estresse Psicológico/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/psicologia , Feminino , Humanos , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia
6.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445300

RESUMO

Type 2 diabetes mellitus is a widespread medical condition, characterized by high blood glucose and inadequate insulin action, which leads to insulin resistance. Insulin resistance in insulin-responsive tissues precedes the onset of pancreatic ß-cell dysfunction. Multiple molecular and pathophysiological mechanisms are involved in insulin resistance. Insulin resistance is a consequence of a complex combination of metabolic disorders, lipotoxicity, glucotoxicity, and inflammation. There is ample evidence linking different mechanistic approaches as the cause of insulin resistance, but no central mechanism is yet described as an underlying reason behind this condition. This review combines and interlinks the defects in the insulin signal transduction pathway of the insulin resistance state with special emphasis on the AGE-RAGE-NF-κB axis. Here, we describe important factors that play a crucial role in the pathogenesis of insulin resistance to provide directionality for the events. The interplay of inflammation and oxidative stress that leads to ß-cell decline through the IAPP-RAGE induced ß-cell toxicity is also addressed. Overall, by generating a comprehensive overview of the plethora of mechanisms involved in insulin resistance, we focus on the establishment of unifying mechanisms to provide new insights for the future interventions of type 2 diabetes mellitus.


Assuntos
Resistência à Insulina/fisiologia , Insulina/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia
7.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199458

RESUMO

As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations. The naked mole rats (NMR) are from eastern Africa and can live for over three decades in chronically hypoxic environments. Despite their long lifespan, NMRs show little to no biological decline, neurodegeneration, or senescence. Here, we discuss molecular pathways and adaptations that NMRs employ to maintain genome integrity and combat the physiological and pathological decline in organismal function.


Assuntos
Adaptação Fisiológica/genética , Senescência Celular/genética , Dano ao DNA/genética , Estresse Oxidativo/genética , Envelhecimento/genética , Animais , DNA/genética , Homeostase , Ratos-Toupeira/genética , Estresse Oxidativo/fisiologia
8.
BMC Neurol ; 21(1): 258, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215195

RESUMO

BACKGROUND: Stroke is a major cause of mortality and morbidity. Also, free radicals and oxidative stress are deleterious factor in the stroke progression. We aimed to evaluate the association between oxidative stress markers and odds of having risk factor for stroke or developing stroke. METHODS: The present case-control study was conducted on 556 participants in Imam-Reza hospital, Tabriz, Iran. Subjects were divided into three group, including individuals with acute ischemic stroke, those who were at risk of stroke, and healthy controls. All enrolled participants except for controls underwent neurological examinations and brain magnetic resonance imaging (MRI). Stroke-related disability and stroke severity were evaluated by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS), respectively. Serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were measured within 48 h of the initiation of stroke. One-way ANOVA and Chi-square tests were used for comparing characteristics between groups. Multivariable logistic regression was implemented for odds of stroke based on MDA and TAC quartiles. Also, Spearman's correlation was utilized. RESULTS: Serum MDA, systolic and diastolic blood pressure, cholesterol, and triglyceride were significantly higher in the stroke group than controls. High levels of MDA were associated with increased development of stroke (P-value < 0.001), however TAC and MDA were not associated with having risk factors for stroke (P-value = 1.00 and 0.27, respectively). Also, TAC level was negatively associated with baseline (ρ = - 0.28; P-value = 0.04) and follow-up (ρ = - 0.31; P-value = 0.03) NIHSS scores. Moreover, MDA was correlated with mRS score at follow-up (ρ = - 0.26; P-value = 0.04). CONCLUSIONS: The balance between antioxidants and oxidants markers might reveal a new approach in this context. Further studies are warranted to identify the source of oxidative stress as well as cessation of the production of oxygen radicals in stroke.


Assuntos
AVC Isquêmico , Estresse Oxidativo/fisiologia , Antioxidantes/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Prognóstico , Fatores de Risco
9.
Molecules ; 26(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34299433

RESUMO

We investigated flavonoid accumulation and lipid peroxidation in young leaves (YL) and mature leaves (ML) of Arabidopsis thaliana plants, whose watering stopped 24 h before sampling, characterized as onset of drought stress (OnDS), six days before sampling, characterized as mild drought stress (MiDS), and ten days before sampling, characterized as moderate drought stress (MoDS). The response to drought stress (DS) of photosystem II (PSII) photochemistry, in both leaf types, was evaluated by estimating the allocation of absorbed light to photochemistry (ΦPSII), to heat dissipation by regulated non-photochemical energy loss (ΦNPQ) and to non-regulated energy dissipated in PSII (ΦNO). Young leaves were better protected at MoDS than ML leaves, by having higher concentration of flavonoids that promote acclimation of YL PSII photochemistry to MoDS, showing lower lipid peroxidation and excitation pressure (1 - qp). Young leaves at MoDS possessed lower 1 - qp values and lower excess excitation energy (EXC), not only compared to MoDS ML, but even to MiDS YL. They also possessed a higher capacity to maintain low ΦNO, suggesting a lower singlet oxygen (1O2) generation. Our results highlight that leaves of different developmental stage may display different responses to DS, due to differential accumulation of metabolites, and imply that PSII photochemistry in Arabidopsis thaliana may not show a dose dependent DS response.


Assuntos
Flavonoides/química , Estresse Oxidativo/fisiologia , Complexo de Proteína do Fotossistema II/química , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Clorofila/metabolismo , Secas , Flavonoides/metabolismo , Fluorescência , Luz , Peroxidação de Lipídeos/fisiologia , Oxigênio/metabolismo , Fotoquímica , Fotossíntese , Folhas de Planta/química , Espécies Reativas de Oxigênio , Água/metabolismo
10.
Biomolecules ; 11(7)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209255

RESUMO

Various environmental stimuli, including oxidative stress, could lead to granulosa cell (GC) death through mitophagy. Recently, it was reported that melatonin (MEL) has a significant effect on GC survival during oxidative damage. Here, we found that MEL inhibited oxidative stress-induced mitophagy to promote GC survival. The loss of cell viability upon H2O2 exposure was significantly restored after MEL treatment. Concomitantly, MEL inhibited the activation of mitophagy during oxidative stress. Notably, blocking mitophagy repressed GC death caused by oxidative stress. However, MEL cannot further restore viability of cells treated with mitophagy inhibitor. Moreover, PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase, was inhibited by MEL during oxidative stress. As a result, the E3 ligase Parkin failed to translocate to mitochondria, leading to impaired mitochondria clearance. Using RNAi to knock down PINK1 expression, we further verified the role of the MEL-PINK1-Parkin (MPP) pathway in maintaining GC survival by suppressing mitophagy. Our findings not only clarify the protective mechanisms of MEL against oxidative damage in GCs, but also extend the understanding about how circadian rhythms might influence follicles development in the ovary. These findings reveal a new mechanism of melatonin in defense against oxidative damage to GCs by repressing mitophagy, which may be a potential therapeutic target for anovulatory disorders.


Assuntos
Células da Granulosa/metabolismo , Melatonina/farmacologia , Mitofagia/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células da Granulosa/fisiologia , Peróxido de Hidrogênio/farmacologia , Masculino , Melatonina/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/farmacologia , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
11.
Biomed Pharmacother ; 141: 111922, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34323703

RESUMO

The Coronavirus disease 19 (Covid-19) pandemic is devastating the public health: it is urgent to find a viable therapy to reduce the multiorgan damage of the disease. A validated therapeutic protocol is still missing. The most severe forms of the disease are related to an exaggerated inflammatory response. The pivotal role of reactive oxygen species (ROS) in the amplification of inflammation makes the antioxidants a potential therapy, but clinical trials are needed. The lecitinized superoxide dismutase (PC-SOD) could represent a possibility because of bioaviability, safety, and its modulatory effect on the innate immune response in reducing the harmful consequences of oxidative stress. In this review we summarize the evidence on lecitinized superoxide dismutase in animal and human studies, to highlight the rationale for using the PC-SOD to treat COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilcolinas/uso terapêutico , Superóxido Dismutase/uso terapêutico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , COVID-19/diagnóstico , COVID-19/metabolismo , Humanos , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/metabolismo , Estresse Oxidativo/fisiologia , Pandemias , Fosfatidilcolinas/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/farmacologia
12.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281188

RESUMO

Endometriosis is a disease of reproductive age characterized by chronic pelvic pain and infertility. Its pathogenesis is complex and still partially unexplained. However, there is increasing evidence of the role of chronic inflammation, immune system dysregulation, and oxidative stress in its development and progression. The latter appears to be involved in multiple aspects of the disease. Indeed, disease progression sustained by a hyperproliferative phenotype can be related to reactive oxygen species (ROS) imbalance, as numerous experiments using drugs to counteract hyperproliferation have shown in recent years. Chronic pelvic pain is also associated with cell function dysregulation favoring chronic inflammation and oxidative stress, specifically involving macrophages and mast cell activation. Moreover, there is increasing evidence of a role for ROS and impaired mitochondrial function not only as deleterious effectors of the ovarian reserve in patients with endometriomas but also in terms of oocyte quality and, hence, embryo development impairment. Targeting oxidative stress looks to be a promising strategy to both curb endometriotic lesion progression and alleviate endometriosis-associated symptoms of chronic pain and infertility. More investigations are nevertheless needed to develop effective therapeutic strategies for clinical application.


Assuntos
Endometriose/metabolismo , Endometriose/terapia , Estresse Oxidativo/fisiologia , Antioxidantes/uso terapêutico , Endometriose/patologia , Feminino , Humanos , Infertilidade Feminina/etiologia , Oócitos/patologia , Dor Pélvica/etiologia , Espécies Reativas de Oxigênio , Reprodução/fisiologia
13.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199527

RESUMO

Overactive bladder (OAB) syndrome, including frequency, urgency, nocturia and urgency incontinence, has a significantly negative impact on the quality-of-life scale (QoL) and can cause sufferer withdrawal from social activities. The occurrence of OAB can result from an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidant-induced oxidative stress. Several animal models, such as bladder ischemia/reperfusion (I/R), partial bladder outlet obstruction (PBOO) and ovarian hormone deficiency (OHD), have suggested that cyclic I/R during the micturition cycle induces oxidative stress, leading to bladder denervation, bladder afferent pathway sensitization and overexpression of bladder-damaging molecules, and finally resulting in bladder hyperactivity. Based on the results of previous animal experiments, the present review specifically focuses on four issues: (1) oxidative stress and antioxidant defense system; (2) oxidative stress in OAB and biomarkers of OAB; (3) OAB animal model; (4) potential nature/plant antioxidant treatment strategies for urinary dysfunction with OAB. Moreover, we organized the relationships between urinary dysfunction and oxidative stress biomarkers in urine, blood and bladder tissue. Reviewed information also revealed the summary of research findings for the effects of various antioxidants for treatment strategies for OAB.


Assuntos
Antioxidantes/uso terapêutico , Isquemia/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Humanos , Isquemia/patologia , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Incontinência Urinária/patologia
14.
Gene ; 799: 145824, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34252531

RESUMO

The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.


Assuntos
Proteínas de Transporte de Cátions/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Proteínas de Xenopus/fisiologia , Zinco/metabolismo , Animais , Transtorno Autístico/metabolismo , Bancos de Espécimes Biológicos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Pulmão/fisiopatologia , Família Multigênica , Doenças Neurodegenerativas/etiologia , Estresse Oxidativo/fisiologia , Reino Unido , Vertebrados/genética
15.
Biomed Pharmacother ; 139: 111691, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243613

RESUMO

Lifestyle modifications such as increase in high-fat food consumption importantly increases the risks for cardiovascular disease. The principal objective of this study is to analyze effects of different high fat diet (HFD) sources on haemodynamic parameters, lipid and oxidative profile, myeloperoxidase activity, and markers of inflammation (IL-6/pentraxin-3). HFD containing 20% of fat, provided by lard (saturated) or soybean oil (unsaturated), as well as control diet were administering to three groups (L, SO and C). Food efficiency ratio and plasma lipids were significantly elevated in both HFD groups. However, only SO group showed an increase in systolic arterial pressure, oxidative stress index, myeloperoxidase activity, liver lipids as well as markers of inflammation: IL-6 and pentraxin-3 (PTX3). In summary, these results indicate inflammogenic potential of excessive soybean oil consumption in triggering liver damage.


Assuntos
Ácidos Graxos Insaturados/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo/fisiologia , Animais , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Interleucina-6/metabolismo , Fígado/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Componente Amiloide P Sérico/metabolismo , Óleo de Soja/efeitos adversos
16.
Molecules ; 26(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207619

RESUMO

Trypanosoma cruzi is the etiologic agent for Chagas disease, which affects 6-7 million people worldwide. The biological diversity of the parasite reflects on inefficiency of benznidazole, which is a first choice chemotherapy, on chronic patients. ABC transporters that extrude xenobiotics, metabolites, and mediators are overexpressed in resistant cells and contribute to chemotherapy failure. An ABCC-like transport was identified in the Y strain and extrudes thiol-conjugated compounds. As thiols represent a line of defense towards reactive species, we aimed to verify whether ABCC-like transport could participate in the regulation of responses to stressor stimuli. In order to achieve this, ABCC-like activity was measured by flow cytometry using fluorescent substrates. The present study reveals the participation of glutathione and ceramides on ABCC-like transport, which are both implicated in stress. Hemin modulated the ABCC-like efflux which suggests that this protein might be involved in cellular detoxification. Additionally, all strains evaluated exhibited ABCC-like activity, while no ABCB1-like activity was detected. Results suggest that ABCC-like efflux is not associated with natural resistance to benznidazole, since sensitive strains showed higher activity than the resistant ones. Although benznidazole is not a direct substrate, ABCC-like efflux increased after prolonged drug exposure and this indicates that the ABCC-like efflux mediated protection against cell stress depends on the glutathione biosynthesis pathway.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Doença de Chagas/tratamento farmacológico , Glutationa/metabolismo , Nitroimidazóis/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Transporte Biológico , Doença de Chagas/parasitologia , Resistência a Medicamentos , Estresse Oxidativo/fisiologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/metabolismo
17.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299254

RESUMO

The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel. In cells, the production of ADP-ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2-dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases.


Assuntos
Células Endoteliais/metabolismo , Canais de Cátion TRPM/metabolismo , Adenosina Difosfato Ribose/metabolismo , Animais , Cálcio/metabolismo , Morte Celular , Movimento Celular , Células Endoteliais/fisiologia , Humanos , Ativação do Canal Iônico/fisiologia , Estresse Oxidativo/fisiologia , Pirofosfatases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/fisiologia
18.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298913

RESUMO

Up to 11% of pregnancies extend to post-term with adverse obstetric events linked to pregnancies over 42 weeks. Oxidative stress and senescence (cells stop growing and dividing by irreversibly arresting their cell cycle and gradually ageing) can result in diminished cell function. There are no detailed studies of placental cell senescence markers across a range of gestational ages, although increased levels have been linked to pre-eclampsia before full term. This study aimed to determine placental senescence and oxidative markers across a range of gestational ages in women with uncomplicated pregnancies and those with a diagnosis of pre-eclampsia. Placentae were obtained from 37 women with uncomplicated pregnancies of 37-42 weeks and from 13 cases of pre-eclampsia of 31+2-41+2 weeks. The expression of markers of senescence, oxidative stress, and antioxidant defence (tumour suppressor protein p16INK4a, kinase inhibitor p21, interleukin-6 (IL-6), NADPH oxidase 4 (NOX4), glutathione peroxidases 1, 3, and 4 (GPx1, GPx3, and GPx4), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1)) genes was measured (quantitative real-time PCR). Protein abundance of p16INK4a, IL-6, NOX4, 8-hydroxy-2'-deoxy-guanosine (8-OHdG), and PlGF was assessed by immunocytochemistry. Placental NOX4 protein was higher in post-term than term deliveries and further increased by pre-eclampsia (p < 0.05 for all). P21 expression was higher in post-term placentae (p = 0.012) and in pre-eclampsia (p = 0.04), compared to term. Placental P16INK4a protein expression was increased post-term, compared to term (p = 0.01). In normotensive women, gestational age at delivery was negatively associated with GPx4 and PlGF (mRNA and protein) (p < 0.05 for all), whereas a positive correlation was seen with placental P21, NOX4, and P16INK4a (p < 0.05 for all) expression. Markers of placental oxidative stress and senescence appear to increase as gestational age increases, with antioxidant defences diminishing concomitantly. These observations increase our understanding of placental health and may contribute to assessment of the optimal gestational age for delivery.


Assuntos
Senescência Celular/fisiologia , Estresse Oxidativo/fisiologia , Placenta/fisiologia , Pré-Eclâmpsia/fisiopatologia , Adulto , Biomarcadores/metabolismo , Feminino , Idade Gestacional , Humanos , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Resultado da Gravidez , RNA Mensageiro/metabolismo
19.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203484

RESUMO

Chronic diseases represent a major challenge in world health. Metabolic syndrome is a constellation of disturbances affecting several organs, and it has been proposed to be a liver-centered condition. Fructose overconsumption may result in insulin resistance, oxidative stress, inflammation, elevated uric acid levels, increased blood pressure, and increased triglyceride concentrations in both the blood and liver. Non-alcoholic fatty liver disease (NAFLD) is a term widely used to describe excessive fatty infiltration in the liver in the absence of alcohol, autoimmune disorders, or viral hepatitis; it is attributed to obesity, high sugar and fat consumption, and sedentarism. If untreated, NAFLD can progress to nonalcoholic steatohepatitis (NASH), characterized by inflammation and mild fibrosis in addition to fat infiltration and, eventually, advanced scar tissue deposition, cirrhosis, and finally liver cancer, which constitutes the culmination of the disease. Notably, fructose is recognized as a major mediator of NAFLD, as a significant correlation between fructose intake and the degree of inflammation and fibrosis has been found in preclinical and clinical studies. Moreover, fructose is a risk factor for liver cancer development. Interestingly, fructose induces a number of proinflammatory, fibrogenic, and oncogenic signaling pathways that explain its deleterious effects in the body, especially in the liver.


Assuntos
Frutose/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Animais , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/fisiologia , Ácido Úrico/metabolismo
20.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209800

RESUMO

Diabetes mellitus (DM) is a chronic metabolic disease characterised by insulin deficiency, resulting in hyperglycaemia, a characteristic symptom of type 2 diabetes mellitus (DM2). DM substantially affects numerous metabolic pathways, resulting in ß-cell dysfunction, insulin resistance, abnormal blood glucose levels, impaired lipid metabolism, inflammatory processes, and excessive oxidative stress. Oxidative stress can affect the body's normal physiological function and cause numerous cellular and molecular changes, such as mitochondrial dysfunction. Animal models are useful for exploring the cellular and molecular mechanisms of DM and improving novel therapeutics for their safe use in human beings. Due to their health benefits, there is significant interest in a wide range of natural compounds that can act as naturally occurring anti-diabetic compounds. Due to rodent models' relatively similar physiology to humans and ease of handling and housing, they are widely used as pre-clinical models for studying several metabolic disorders. In this review, we analyse the currently available rodent animal models of DM and their advantages and disadvantages and highlight the potential anti-oxidative effects of natural compounds and their mechanisms of action.


Assuntos
Produtos Biológicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Produtos Biológicos/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Estresse Oxidativo/fisiologia , Roedores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...