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1.
Braz. j. biol ; 84: e249617, 2024. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345540

RESUMO

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.


Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.


Assuntos
Animais , Hibernação , Lagartos , Oxirredução , Estresse Oxidativo , Eritrócitos
2.
Braz. j. biol ; 84: e254010, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345561

RESUMO

Abstract The impact of fish oil concentration on the oxidative stability of microcapsules through the spray drying process using chitosan and maltodextrin as wall material was studied. Emulsions were prepared with different Tuna fish oil (TFO) content (TFO-10%, TFO20%, TF030% TF0-40%) while wall material concentration was kept constant. Microencapsulated powder resulting from emulsion prepared with high fish oil load have high moisture content, wettability, total oil and low encapsulation efficiency, hygroscopicity and bulk tapped density. Oxidative stability was evaluated periodically by placing microcapsules at room temperature. Microcapsules prepared with TFO-10% presented high oxidative stability in terms of peroxide value (2.94±0.04) and anisidine value (1.54±0.02) after 30 days of storage. It was concluded that optimal amounts of fish oil for microencapsulation are 10% and 20% using chitosan and maltodextrin that extended its shelf life during study period.


Resumo Foi estudado o impacto da concentração de óleo de peixe na estabilidade oxidativa de microcápsulas por meio do processo de secagem por atomização, utilizando quitosana e maltodextrina como material de parede. As emulsões foram preparadas com diferentes teores de óleo de atum (TFO) (TFO-10%, TFO20%, TF030% TF0-40%), enquanto a concentração de material de parede foi mantida constante. O pó microencapsulado resultante da emulsão preparada com alta carga de óleo de peixe tem alto teor de umidade, molhabilidade e óleo total e baixa eficiência de encapsulação, higroscopicidade e densidade extraída a granel. A estabilidade oxidativa foi avaliada periodicamente colocando microcápsulas à temperatura ambiente. As microcápsulas preparadas com TFO-10% apresentaram alta estabilidade oxidativa em termos de valor de peróxido (2,94 ± 0,04) e valor de anisidina (1,54 ± 0,02) após 30 dias de armazenamento. Concluiu-se que as quantidades ideais de óleo de peixe para microencapsulação são de 10% e 20% usando quitosana e maltodextrina que prolongaram sua vida útil durante o período de estudo.


Assuntos
Animais , Óleos de Peixe , Quitosana , Pós , Atum , Estresse Oxidativo
3.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633130

RESUMO

Oxidative stress and neuroapoptosis are key pathological processes after subarachnoid hemorrhage (SAH). The present study evaluated the anti­oxidation and anti­apoptotic neuroprotective effects of the apoptosis signal­regulating kinase 1 (ASK1) inhibitor ethyl­2,7­dioxo­2,7­dihydro­3H­naphtho(1,2,3­de)quinoline­1­carboxylate (NQDI­1) in early brain injury (EBI) following SAH in a rat model. A total of 191 rats were used and the SAH model was induced using monofilament perforation. Western blotting was subsequently used to detect the endogenous expression levels of proteins. Immunofluorescence was then used to confirm the nerve cellular localization of ASK1. Short­term neurological function was assessed using the modified Garcia scores and the beam balance test 24 h after SAH, whereas long­term neurological function was assessed using the rotarod test and the Morris water maze test. Apoptosis of neurons was assessed by TUNEL staining and oxidative stress was assessed by dihydroethidium staining 24 h after SAH. The protein expression levels of phosphorylated (p­)ASK1 and ASK1 rose following SAH. NQDI­1 was intracerebroventricularly injected 1 h after SAH and demonstrated significant improvements in both short and long­term neurological function and significantly reduced oxidative stress and neuronal apoptosis. Injection of NQDI­1 caused a significant decrease in protein expression levels of p­ASK1, p­p38, p­JNK, 4 hydroxynonenal, and Bax and significantly increased the protein expression levels of heme oxygenase 1 and Bcl­2. The use of the p38 inhibitor BMS­582949 or the JNK inhibitor SP600125 led to significant decreases in the protein expression levels of p­p38 or p­JNK, respectively, and a significant reduction in oxidative stress and neuronal apoptosis; however, these inhibitors did not demonstrate an effect on p­ASK1 or ASK1 protein expression levels. In conclusion, treatment with NQDI­1 improved neurological function and decreased oxidative stress and neuronal apoptosis in EBI following SAH in rats, possibly via inhibition of ASK1 phosphorylation and the ASK1/p38 and JNK signaling pathway. NQDI­1 may be considered a potential agent for the treatment of patients with SAH.


Assuntos
Lesões Encefálicas , Fármacos Neuroprotetores , Hemorragia Subaracnóidea , Ratos , Animais , Sistema de Sinalização das MAP Quinases , Ratos Sprague-Dawley , MAP Quinase Quinase Quinase 5/metabolismo , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Apoptose , Estresse Oxidativo , Fármacos Neuroprotetores/farmacologia
4.
Ultrastruct Pathol ; 47(1): 12-21, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36588172

RESUMO

Calanus oil, an oil extracted from the marine crustacean Calanus finmarchicus, is one of the richest sources of omega-3 and poly-unsaturated fatty acids. Although calanus oil has been shown to have a significant anti-hypertensive, anti-inflammatory, anti-fibrotic and anti-obesity effects in various cardiovascular diseases, but little is known about its effect on pathological cardiac hypertrophy. Thus, the present study was carried out to evaluate the therapeutic effect of calanus oil on cardiac hypertrophy. Cardiac hypertrophy was induced by subcutaneous injections with isoproterenol (5 mg/kg b.w) for 14 consecutive days. Calanus oil (400 mg/kg) was given orally for 4 weeks. Cardiac pathological remodeling was evaluated by echocardiography, after which morphometric, biochemical, histological and ultrastructural analyses were performed. Calanus oil treatment significantly ameliorated isoproterenol-induced structural and functional alterations in echocardiography. Calanus oil also reduced the relative heart weight, significantly decreased the elevated cardiac enzymes (LDH and CK-MB) and the lipid peroxidation marker (MDA), augmented the myocardial antioxidant status (TAC), and ameliorated the histopathological and ultrastructural changes in cardiac tissues and prevented interstitial collagen deposition. The present study, for the first time, provided morphometric, biochemical, histological and ultrastructural evidences supporting the promising anti-hypertrophic effect of calanus oil against ISO-induced cardiac hypertrophy. This anti-hypertrophic effect of calanus oil is via regulating myocardial remodeling and oxidative stress. Therefore, it could be used as potential pharmacological intervention in the management of cardiac hypertrophy.


Assuntos
Miocárdio , Estresse Oxidativo , Humanos , Isoproterenol/toxicidade , Isoproterenol/metabolismo , Miocárdio/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controle , Cardiomegalia/patologia , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia
5.
Cell Transplant ; 32: 9636897221147920, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594258

RESUMO

Mesenchymal stem cells (MSCs) have gained interest as an alternative therapeutic option for renal diseases, including acute kidney injury (AKI). However, their use is often limited owing to low survival rates in vivo. Fenoldopam mesylate (FD) is a selective dopamine D1 receptor agonist with antioxidative and anti-apoptotic roles. Herein, we investigated whether FD can enhance the survival of MSCs undergoing oxidative stress in vitro. In addition, the therapeutic effect of MSCs and FD-treated MSCs (FD-MSCs) was compared in a mouse model of AKI induced by cisplatin. The survival of MSCs under oxidative stress was augmented by FD treatment. FD induced the phosphorylation of cAMP response element-binding protein and AKT, contributing to enhanced growth compared with untreated MSCs. The expression of nuclear factor erythroid-2-related factor 2 (NRF2) and heme oxygenase-1 was increased by FD treatment, and nuclear translocation of NRF2 was found exclusively in FD-MSCs. FD downregulated BAX expression, increased the mitochondrial membrane potential, reduced reactive oxygen species generation, and decreased the apoptotic death of MSCs induced by oxidative stress. Moreover, renal function and tubular injury were improved in FD-MSCs compared with non-treated MSCs. Furthermore, tubular injury, apoptosis, and macrophage infiltration, as well as the serum level of tumor necrosis factor-α were reduced, while tubular cell proliferation was markedly increased in FD-MSCs compared with MSCs. Our study demonstrated that FD increases the survivability of MSCs in an oxidative environment, and its use may be effective in preparing robust therapeutic MSCs.


Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Camundongos , Animais , Fenoldopam/efeitos adversos , Fenoldopam/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Injúria Renal Aguda/terapia , Injúria Renal Aguda/patologia , Estresse Oxidativo
6.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614174

RESUMO

The research on new treatments for dry eye diseases (DED) has exponentially grown over the past decades. The increased prevalence of dry eye conditions, particularly in the younger population, has received much attention. Therefore, it is of utmost importance to identify novel therapeutical targets. Regulated cell death (RCD) is an essential process to control the biological homeostasis of tissues and organisms. The identification of different mechanisms of RCD stimulated the research on their involvement in different human pathologies. Whereas apoptosis has been widely studied in DED and included in the DED vicious cycle, the role of RCD still needs to be completely elucidated. In this review, we will explore the potential roles of different types of RCD in DED and ocular surface dysfunction. Starting from the evidence of oxidative stress and inflammation in dry eye pathology, we will analyse the potential therapeutic applications of the following principal RCD mechanisms: ferroptosis, necroptosis, and pyroptosis.


Assuntos
Síndromes do Olho Seco , Morte Celular Regulada , Humanos , Síndromes do Olho Seco/metabolismo , Inflamação , Apoptose , Estresse Oxidativo
7.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614263

RESUMO

Since brown rice extract is a rich source of biologically active compounds, the present study is aimed to quantify the major compounds in brown rice and to compare their cytoprotective potential against oxidative stress. The content of the main hydrophobic compounds in brown rice followed the order of cycloartenyl ferulate (CAF) (89.00 ± 8.07 nmol/g) >> α-tocopherol (αT) (19.73 ± 2.28 nmol/g) > γ-tocotrienol (γT3) (18.24 ± 1.41 nmol/g) > α-tocotrienol (αT3) (16.02 ± 1.29 nmol/g) > γ-tocopherol (γT) (3.81 ± 0.40 nmol/g). However, the percent contribution of CAF to the radical scavenging activity of one gram of whole brown rice was similar to those of αT, αT3, and γT3 because of its weaker antioxidant activity. The CAF pretreatment displayed a significant cytoprotective effect on the hydrogen peroxide-induced cytotoxicity from 10 µM, which is lower than the minimal concentrations of αT and γT required for a significant protection. CAF also enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation coincided with the enhancement of the heme oxygenase-1 (HO-1) mRNA level. An HO-1 inhibitor, tin protoporphyrin IX (SnPP), significantly impaired the cytoprotection of CAF. The cytoprotective potential of CAF is attributable to its cycloartenyl moiety besides the ferulyl moiety. These results suggested that CAF is the predominant cytoprotector in brown rice against hydrogen peroxide-induced cytotoxicity.


Assuntos
Oryza , Oryza/metabolismo , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , alfa-Tocoferol/farmacologia , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo
8.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614301

RESUMO

Redox regulation participates in the control of various aspects of metabolism. Reactive oxygen and nitrogen species participate in many reactions under physiological conditions. When these species overcome the antioxidant defense system, a distressed status emerges, increasing biomolecular damage and leading to functional alterations. Air pollution is one of the exogenous sources of reactive oxygen and nitrogen species. Ambient airborne particulate matter (PM) is important because of its complex composition, which includes transition metals and organic compounds. Once in contact with the lungs' epithelium, PM components initiate the synthesis of inflammatory mediators, macrophage activation, modulation of gene expression, and the activation of transcription factors, which are all related to the physiopathology of chronic respiratory diseases, including cancer. Even though the pathophysiological pathways that give rise to the development of distress and biological damage are not fully understood, scientific evidence indicates that redox-dependent signaling pathways are involved. This article presents an overview of the redox interaction of air pollution inside the human body and the courses related to chronic respiratory diseases.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Transtornos Respiratórios , Humanos , Estresse Oxidativo , Poluição do Ar/efeitos adversos , Material Particulado/efeitos adversos , Material Particulado/análise , Oxigênio , Poluentes Atmosféricos/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo
9.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614330

RESUMO

Oxidative stress and immune response play an important role in the development of several cancers, including melanoma. Ion channels are aberrantly expressed in tumour cells and regulate neoplastic transformation, malignant progression, and resistance to therapy. Ion channels are localized in the plasma membrane or other cellular membranes and are targets of oxidative stress, which is particularly elevated in melanoma. At the same time, ion channels are crucial for normal and cancer cell physiology and are subject to multiple layers of regulation, and therefore represent promising targets for therapeutic intervention. In this review, we analyzed the effects of oxidative stress on ion channels on a molecular and cellular level and in the context of melanoma progression and immune evasion. The possible role of ion channels as targets of alternative therapeutic strategies in melanoma was discussed.


Assuntos
Canais Iônicos , Melanoma , Humanos , Canais Iônicos/metabolismo , Melanoma/tratamento farmacológico , Transformação Celular Neoplásica/metabolismo , Imunidade , Estresse Oxidativo
10.
Cardiovasc Toxicol ; 23(1): 61-73, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36648739

RESUMO

Cardiovascular diseases (CVDs) are known as the first causes of death throughout the world, and mainly myocardial infarction (MI), lead to 7.4 million deaths annually. Atherosclerosis is the major underlying cause of most CVDs. However, exposure to heavy metals, among other factors, deserves further attention as a risk factor for CVDs. This study was designed to evaluate the levels of arsenic (Ars) in myocardial infarction (MI) patients and healthy individuals as well as assess the association between the incidence of MI and Ars, total antioxidant capacity (TAC), and oxidative stress. This case-control study was conducted among patients with MI (n = 164) and normal individuals (n = 61) at Shafa Hospital in Kerman, Iran. Patients were classified into two groups, including coronary artery blocks above 50% (CAB > 50%, n = 83) and coronary artery blocks less than 50% (CAB < 50%, n = 83) based on their angiography findings. The demographic characteristics, clinical history, biochemical parameters, and serum Ars and TAC levels were evaluated. In the present study, both CAB groups had significantly reduced levels of TAC compared with the control. Furthermore, TAC was lower in the CAB > %50 group compared to the CAB < %50 group. Ars levels were significantly higher in both CAB groups compared with the control. There was a significant positive relationship between CAB and Ars, BG, HbA1c, urea, creatinine, TG, TC, and LDL-c, as well as a negative relationship between HDL-c and TAC. Moreover, TAC levels showed a significant inverse correlation with Ars, HbA1c, and creatinine, and a positive correlation with HDL-c. As risk factors, Ars, hs-CRP, TG, TC, and LDL-c enhance the severity of the disease, and HDL-c and TAC decrease the disease severity. Moreover, ROC curve analysis revealed that the highest AUC for the CAB > %50 (AUC = 78.29), and cytotoxic levels for both CAB groups (Ars ≥ 0.105 ppm), and no significant differences were found between the two groups. Our findings suggest that Ars at ≥ 0.105 ppm is able to increase the risk of MI through the increased OS and decreased TAC.


Assuntos
Arsênio , Infarto do Miocárdio , Humanos , Arsênio/efeitos adversos , Estudos de Casos e Controles , LDL-Colesterol , Creatinina , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Estresse Oxidativo , Antioxidantes
11.
Cardiovasc Toxicol ; 23(1): 46-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650404

RESUMO

Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1ß (IL-1ß) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Cuprizona , Ratos , Masculino , Animais , Ratos Wistar , Catalase/metabolismo , Cuprizona/metabolismo , Cuprizona/farmacologia , Cuprizona/uso terapêutico , Cardiotoxicidade/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Fígado/patologia , Anti-Inflamatórios/uso terapêutico
12.
J Enzyme Inhib Med Chem ; 38(1): 2166937, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36651294

RESUMO

Thioredoxin interacting protein (TXNIP) is a potential drug target for type 2 diabetes mellitus (T2DM) treatment. A series of quinazoline derivatives were designed, synthesised, and evaluated to inhibit TXNIP expression and protect from palmitate (PA)-induced ß cell injury. In vitro cell viability assay showed that compounds D-2 and C-1 could effectively protect ß cell from PA-induced apoptosis, and subsequent results showed that these two compounds decreased TXNIP expression by accelerating its protein degradation. Mechanistically, compounds D-2 and C-1 reduced intracellular reactive oxygen species (ROS) production and modulated TXNIP-NLRP3 inflammasome signalling, and thus alleviating oxidative stress injury and inflammatory response under PA insult. Besides, these two compounds were predicted to possess better drug-likeness properties using SwissADME. The present study showed that compounds D-2 and C-1, especially compound D-2, were potent pancreatic ß cell protective agents to inhibit TXNIP expression and might serve as promising lead candidates for the treatment of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Linhagem Celular , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transporte/farmacologia
13.
Toxicol Appl Pharmacol ; 460: 116375, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36634873

RESUMO

Estrogen contributes to the development of breast cancer through estrogen receptor (ER) signaling and by generating genotoxic metabolites that cause oxidative DNA damage. To protect against oxidative stress, cells activate nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream cytoprotective genes that initiate antioxidant responses and detoxify xenobiotics. Nrf2 activation occurs by inhibiting the protein-protein interaction (PPI) between Nrf2 and its inhibitor Keap1, which otherwise targets Nrf2 for ubiquitination and destruction. In this study, we examined a series of novel direct inhibitors of Keap1-Nrf2 PPI in their role in promoting the availability of Nrf2 for antioxidant activity and attenuating estrogen-mediated responses in breast cancer. ER-positive human breast cancer cells MCF-7 were treated with 17ß-estradiol (E2) in the presence or absence of selected Keap1-Nrf2 PPI inhibitors. Keap1-Nrf2 PPI inhibitors suppressed the mRNA and protein levels of estrogen responsive genes induced by E2 exposure, such as PGR. Keap1-Nrf2 PPI inhibitors caused significant activation of Nrf2 target genes. E2 decreased the mRNA and protein level of the Nrf2 target gene NQO1, and the Keap1-Nrf2 PPI inhibitors reversed this effect. The reversal of E2 action by these compounds was not due to binding to ER as ER antagonists. Further, a selected compound attenuated oxidative stress induced by E2, determined by the level of a biomarker 8-oxo-deoxyguanosine. These findings suggest that the Keap1-Nrf2 PPI inhibitors have potent antioxidant activity by activating Nrf2 pathways and inhibit E2-induced gene and protein expression. These compounds may serve as potential chemopreventive agents in estrogen-stimulated breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Antioxidantes/farmacologia , Receptores de Estrogênio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Estrogênios/farmacologia , RNA Mensageiro/metabolismo , Expressão Gênica
14.
Artigo em Inglês | MEDLINE | ID: mdl-36673654

RESUMO

This study aims to analyse sex-specific associations of physical activity and sedentary behaviour with oxidative stress and inflammatory markers in a young-adult population. Sixty participants (21 women, 22.63 ± 4.62 years old) wore a hip accelerometer for 7 consecutive days to estimate their physical activity and sedentarism. Oxidative stress (catalase, superoxide dismutase, glutathione peroxidase, glutathione, malondialdehyde, and advanced oxidation protein products) and inflammatory (tumour necrosis factor-alpha and interleukin-6) markers were measured. Student t-tests and single linear regressions were applied. The women presented higher catalase activity and glutathione concentrations, and lower levels of advanced protein-oxidation products, tumour necrosis factor-alpha, and interleukin-6 than the men (p < 0.05). In the men, longer sedentary time was associated with lower catalase activity (ß = -0.315, p = 0.04), and longer sedentary breaks and higher physical-activity expenditures were associated with malondialdehyde (ß = -0.308, p = 0.04). Vigorous physical activity was related to inflammatory markers in the women (tumour necrosis factor-alpha, ß = 0.437, p = 0.02) and men (interleukin-6, ß = 0.528, p < 0.01). In conclusion, the women presented a better redox and inflammatory status than the men; however, oxidative-stress markers were associated with physical activity and sedentary behaviours only in the men. In light of this, women could have better protection against the deleterious effect of sedentarism but a worse adaptation to daily physical activity.


Assuntos
Comportamento Sedentário , Fator de Necrose Tumoral alfa , Masculino , Humanos , Feminino , Adulto Jovem , Adolescente , Adulto , Catalase , Interleucina-6 , Exercício Físico , Estresse Oxidativo , Antioxidantes , Malondialdeído , Glutationa , Acelerometria
15.
Molecules ; 28(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36677559

RESUMO

BACKGROUND: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. MATERIALS AND METHODS: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. RESULTS: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. CONCLUSIONS: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/fisiologia , Dieta Hiperlipídica/efeitos adversos , Estreptozocina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Inflamação/tratamento farmacológico , Modelos Animais de Doenças , Estresse Oxidativo , Glucose/farmacologia , Glicemia , Hipoglicemiantes/uso terapêutico
16.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677642

RESUMO

As aging progresses, ß-amyloid (Aß) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). Humulus lupulus L. (hops) is an important medicinal plant widely used in the food, beverage and pharmaceutical industries due to its strong antioxidant ability. In this study, APP/PS1 mutated transgenic mice and Aß-injured osteoblasts were used to evaluate the protective effects of hops extracts (HLE) on SOP. Mice learning and memory levels were assessed by the Morris water maze. Mice femurs were prepared for bone micro-structures and immunohistochemistry experiments. The deposition of Aß in the hippocampus, cortex and femurs were determined by Congo red staining. Moreover, protein expressions related to antioxidant pathways were evaluated by Western blotting. It was found that HLE markedly improved learning abilities and ameliorated memory impairment of APP/PS1 mice, as well as regulated antioxidant enzymes and bone metabolism proteins in mice serum. Micro-CT tests indicated that HLE enhanced BMD and improved micro-architectural parameters of mice femur. More importantly, it was discovered that HLE significantly reduced Aß deposition both in the brain and femur. Further in vitro results showed HLE increased the bone mineralization nodule and reduced the ROS level of Aß-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that Humulus lupulus L. extract could protect against senior osteoporosis through inhibiting Aß deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP.


Assuntos
Doença de Alzheimer , Humulus , Osteoporose , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Camundongos Transgênicos , Humulus/metabolismo , Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Osteoblastos/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Modelos Animais de Doenças
17.
Molecules ; 28(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36677744

RESUMO

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor deficits. The exact etiology of PD is currently unknown; however, the pathological hallmarks of PD include excessive production of reactive oxygen species, enhanced neuroinflammation, and overproduction of α-synuclein. Under normal physiological conditions, aggregated α-synuclein is degraded via the autophagy lysosomal pathway. However, impairment of the autophagy lysosomal pathway results in α-synuclein accumulation, thereby facilitating the pathogenesis of PD. Current medications only manage the symptoms, but are unable to delay, prevent, or cure the disease. Collectively, oxidative stress, inflammation, apoptosis, and autophagy play crucial roles in PD; therefore, there is an enormous interest in exploring novel bioactive agents of natural origin for their protective roles in PD. The present study evaluated the role of myrcene, a monoterpene, in preventing the loss of dopaminergic neurons in a rotenone (ROT)-induced rodent model of PD, and elucidated the underlying mechanisms. Myrcene was administered at a dose of 50 mg/kg, 30 min prior to the intraperitoneal injections of ROT (2.5 mg/kg). Administration of ROT caused a considerable loss of dopaminergic neurons, subsequent to a significant reduction in the antioxidant defense systems, increased lipid peroxidation, and activation of microglia and astrocytes, along with the production of pro-inflammatory cytokines (IL-6, TNF-α, IL-1ß) and matrix metalloproteinase-9. Rotenone also resulted in impairment of the autophagy lysosomal pathway, as evidenced by increased expression of LC3, p62, and beclin-1 with decreased expression in the phosphorylation of mTOR protein. Collectively, these factors result in the loss of dopaminergic neurons. However, myrcene treatment has been observed to restore antioxidant defenses and attenuate the increase in concentrations of lipid peroxidation products, pro-inflammatory cytokines, diminished microglia, and astrocyte activation. Myrcene treatment also enhanced the phosphorylation of mTOR, reinstated neuronal homeostasis, restored autophagy-lysosomal degradation, and prevented the increased expression of α-synuclein following the rescue of dopaminergic neurons. Taken together, our study clearly revealed the mitigating effect of myrcene on dopaminergic neuronal loss, attributed to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties, and favorable modulation of autophagic flux. This study suggests that myrcene may be a potential candidate for therapeutic benefits in PD.


Assuntos
Antioxidantes , Doença de Parkinson , Humanos , Antioxidantes/metabolismo , Rotenona/toxicidade , alfa-Sinucleína/metabolismo , Neurônios Dopaminérgicos , Estresse Oxidativo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Autofagia , Citocinas/metabolismo , Apoptose
18.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677854

RESUMO

This study examined the effect of gold nanoparticles (AuNPs) on doxorubicin (DOX)-induced liver damage and steatosis in rats and tested its effect mechanism. Wistar male rats were divided into four groups (each of eight rats) as control, AuNPs (50 µL of 10 nm), DOX (15 mg/kg; 3 mg/kg/week), and DOX + AuNPs-treated rats. DOX is known to induce fasting hyperglycemia and hyperinsulinemia in treated rats. Individual treatment of both DOX and AuNPs also promoted liver damage, increased circulatory levels of ALT and AST, and stimulated serum and liver levels of TGs, CHOL, LDL-c, and FFAs. They also stimulated MDA, TNF-α, and IL-6, reduced GSH, SOD, HO-1, and CAT, upregulated mRNA levels of Bax and caspases-3 and -8 and downregulated mRNA levels of Bcl2 in the livers of rats. However, while DOX alone reduced hepatic levels of PPARα, both AuNPs and DOX stimulated mRNA levels of SREBP1, reduced the mRNA, cytoplasmic and nuclear levels of Nrf2, and increased mRNA, cytoplasmic, and nuclear levels of NF-κB. The liver damage and the alterations in all these parameters were significantly more profound when both AuNPs and DOX were administered together. In conclusion, AuNPs exaggerate liver damage, hyperlipidemia, and hepatic steatosis in DOX-treated rats by activating SREBP1 and NF-κB and suppressing the Nrf2/antioxidant axis.


Assuntos
Fígado Gorduroso , Hiperlipidemias , Nanopartículas Metálicas , Ratos , Masculino , Animais , Ouro/farmacologia , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , NF-kappa B/metabolismo , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Fígado , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Doxorrubicina/farmacologia
19.
Molecules ; 28(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36677929

RESUMO

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO2) that trigger an immune response in the periprosthetic tissue, leading to arthritis, arthroplasty failure, and the need for revision. Flavonoids belong to a class of natural polyphenolic compounds that possess antioxidant and anti-inflammatory activities. Hesperidin methyl chalcone's (HMC) analgesic, anti-inflammatory, and antioxidant effects have been investigated in some models, but its activity against the arthritis caused by prosthesis-wearing molecules, such as TiO2, has not been investigated. Mice were treated with HMC (100 mg/kg, intraperitoneally (i.p.)) 24 h after intra-articular injection of 3 mg/joint of TiO2, which was used to induce chronic arthritis. HMC inhibited mechanical hyperalgesia, thermal hyperalgesia, joint edema, leukocyte recruitment, and oxidative stress in the knee joint (alterations in gp91phox, GSH, superoxide anion, and lipid peroxidation) and in recruited leukocytes (total reactive oxygen species and GSH); reduced patellar proteoglycan degradation; and decreased pro-inflammatory cytokine production. HMC also reduced the activation of nociceptor-sensory TRPV1+ and TRPA1+ neurons. These effects occurred without renal, hepatic, or gastric damage. Thus, HMC reduces arthritis triggered by TiO2, a component released upon wearing of prosthesis.


Assuntos
Artrite , Chalconas , Hesperidina , Camundongos , Animais , Nociceptores/metabolismo , Chalconas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Artrite/tratamento farmacológico , Estresse Oxidativo , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Hiperalgesia/tratamento farmacológico , Citocinas/metabolismo
20.
Molecules ; 28(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36677938

RESUMO

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Curcumina , Ratos , Masculino , Animais , Ratos Wistar , Curcumina/farmacologia , Curcumina/metabolismo , Estresse Oxidativo , NF-kappa B/metabolismo , Proteína X Associada a bcl-2/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Antioxidantes/metabolismo , Fígado , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
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