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1.
BMC Nephrol ; 24(1): 13, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647052

RESUMO

BACKGROUND: Xanthine oxidase activity has a key role in the development of oxidative stress and progression of cardiovascular diseases. However, the change of xanthine oxidase activity following hemodialysis and its prognostic impact remain uncertain. METHODS: We prospectively included hemodialysis patients who did not take any anti-hyperuricemic agents and measured their xanthine oxidase activity before and after the index hemodialysis. The impact of change in xanthine oxidase activity during hemodialysis on cardiovascular death were investigated. RESULTS: A total of 46 patients (median 72 years old, 29 men) were included. During hemodialysis, a common logarithm of xanthine oxidase activity decreased significantly from 1.16 (0.94, 1.27) to 1.03 (0.80, 1.20) (p < 0.01). Of them, xanthine oxidase activity remained unchanged or increased in 16 patients, who had a greater decrease in blood pressure and more hemoconcentration compared with others. Two-year survival from cardiovascular death was not significantly stratified by the changes in xanthine oxidase activity (p = 0.43). CONCLUSIONS: During hemodialysis, xanthine oxidase activity decreased among the overall cohort, whereas some patients experienced its increases, which might be associated with hypotension and hemoconcentration during hemodialysis. Further larger-scale studies are required to validate our findings and find clinical implication of change in xanthine oxidase activity during hemodialysis.


Assuntos
Estresse Oxidativo , Xantina Oxidase , Idoso , Humanos , Masculino , Pressão Sanguínea , Coração , Estresse Oxidativo/fisiologia , Diálise Renal , Xantina Oxidase/metabolismo , Feminino
2.
Ital J Pediatr ; 49(1): 3, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611205

RESUMO

BACKGROUND: Vitamin B12 is an important vitamin for metabolism and affects many mechanisms in the body including neuronal migration, DNA synthesis, neurotransmitter synthesis, brain and cognitive development. Increased oxidative stress in the body leads to the damage of the child development, but also plays a crucial role in the pathogenesis of many diseases encountered in the childhood period. Our aim is to investigate whether or not B12 deficiency is associated with dynamic thiol/disulfide homeostasis in adolescent patients. METHODS: This is a case-controlled observational study consisting of 45 adolescent patients with vitamin b12 deficiency and a control group consisting of 45 healthy adolescent. Patients between 11 and 18 ages who applied to the outpatient clinic for the first time with one of the complaints of headache were selected due to their decreased school performance, dizziness, and fatigue. Hemogram, vitamin B12, homocysteine levels and oxidative stress parameters such as native and total thiol disulfide levels and ratios of disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were measured from the patients. RESULTS: Vitamin B12 level was found to be significantly lower in vitamin B12 deficiency group (p < 0.001). The serum disulfide level was found to be 27.5 ± 8.38 in the case group and 20.5 ± 8.36 in the control group (p < 0.001). In the multiple linear regression analysis, it was determined that the independent variables of native thiol, homocysteine and disulfide levels effected of vitamin B12 levels (p < 0.001, p < 0.001, p < 0.005 respectively; R2 = 0.62). CONCLUSION: The results obtained in terms of the effect of vitamin B12 deficiency on oxidative stress in adolescents are remarkable. The increase in oxidative stress parameters in the patient group may also suggest that oxidative stress plays a vital role in vitamin B12 deficiency in adolescence.


Assuntos
Dissulfetos , Deficiência de Vitamina B 12 , Criança , Humanos , Adolescente , Compostos de Sulfidrila , Vitaminas , Deficiência de Vitamina B 12/diagnóstico , Vitamina B 12 , Estresse Oxidativo/fisiologia
4.
Vitam Horm ; 121: 197-246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36707135

RESUMO

Hormones have been considered as key factors involved in the maintenance of the redox status of the body. We are making considerable progress in understanding interactions between the endocrine system, redox status, and oxidative stress with the dynamics of life, which encompasses fertilization, development, growth, aging, and various pathophysiological states. One of the reasons for changes in redox states of vertebrates leading to oxidative stress scenario is the disruption of the endocrine system. Comprehending the dynamics of hormonal status to redox state and oxidative stress in living systems is challenging. It is more difficult to come to a unifying conclusion when some hormones exhibit oxidant properties while others have antioxidant features. There is a very limited approach to correlate alteration in titers of hormones with redox status and oxidative stress with growth, development, aging, and pathophysiological stress. The situation is further complicated when considering various tissues and sexes in vertebrates. This chapter discusses the beneficial impacts of hormones with antioxidative properties, such as melatonin, glucagon, insulin, estrogens, and progesterone, which protect cells from oxidative damage and reduce pathophysiological effects. Additionally, we discuss the protective effects of antioxidants like vitamins A, E, and C, curcumin, tempol, N-acetyl cysteine, α-lipoic acid, date palm pollen extract, resveratrol, and flavonoids on oxidative stress triggered by hormones such as aldosterone, glucocorticoids, thyroid hormones, and catecholamines. Inflammation, pathophysiology, and the aging process can all be controlled by understanding how antioxidants and hormones operate together to maintain cellular redox status. Identifying the hormonal changes and the action of antioxidants may help in developing new therapeutic strategies for hormonal imbalance-related disorders.


Assuntos
Antioxidantes , Melatonina , Humanos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Espécies Reativas de Oxigênio/farmacologia , Estresse Oxidativo/fisiologia , Oxirredução , Melatonina/farmacologia
5.
Vitam Horm ; 121: 45-66, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36707143

RESUMO

Reactive oxygen species (ROS), such as hydrogen peroxide, are formed when molecular oxygen obtains additional electrons, increasing its reactivity. While low concentrations of hydrogen peroxide are necessary for regulation of normal cellular signaling events, high concentrations can be toxic. To maintain this balance between beneficial and deleterious concentrations of hydrogen peroxide, cells utilize antioxidants. Our recent work supports a primary role for peroxiredoxin, thioredoxin, and thioredoxin reductase as the oxidant defense pathway used by insulin-producing pancreatic ß-cells. These three players work in an antioxidant cycle based on disulfide exchange, with oxidized targets ultimately being reduced using electrons provided by NADPH. Peroxiredoxins also participate in hydrogen peroxide-based signaling through disulfide exchange with redox-regulated target proteins. This chapter will describe the catalytic mechanisms of thioredoxin, thioredoxin reductase, and peroxiredoxin and provide an in-depth look at the roles these enzymes play in antioxidant defense pathways of insulin-secreting ß-cells. Finally, we will evaluate the physiological relevance of peroxiredoxin-mediated hydrogen peroxide signaling as a regulator of ß-cell function.


Assuntos
Antioxidantes , Insulinas , Humanos , Oxidantes , Peróxido de Hidrogênio/metabolismo , Peroxirredoxinas/metabolismo , Tiorredoxina Dissulfeto Redutase/química , Tiorredoxina Dissulfeto Redutase/metabolismo , Estresse Oxidativo/fisiologia , Tiorredoxinas/metabolismo , Insulinas/metabolismo
6.
Life Sci ; 315: 121358, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36596408

RESUMO

AIMS: The imbalance between reactive oxygen species (ROS) and the antioxidant response has been linked to various airway diseases, including asthma. However, knowledge on cell-specific responses of the airway resident and inflammatory cells against increased oxidant stress is very limited. We aim to better understand the cell-specific antioxidant response that contributes to the pathophysiology of lung disease in response to oxidative stress. MATERIALS AND METHODS: The human cell lines of epithelial, fibroblast, endothelial, monocyte, eosinophil and neutrophil were incubated with tert-butyl hydroperoxide (tBHP) or cigarette smoke condensate (CSC). Following stimulation, cell viability, total oxidant and antioxidant activity were assessed in both residential and inflammatory cells. Human Oxidative Stress Plus RT2 Profiler PCR array was used to determine 84 gene expression differences in oxidant and antioxidant pathways following oxidant stimulus in all cells. KEY FINDINGS: We showed that various cell types respond differently to oxidative stress inducers, with distinct gene expression and oxidant-antioxidant generation. Most importantly, eosinophils increased the activity of all main antioxidant enzymes in response to both oxidants. Monocytes, on the other hand, showed no change in response to each stimulation, whereas neutrophils only increased their CAT activity in response to both stimuli. The increase in NRF2-regulated genes HSPA1A, HMOX1 and DUSP1 after both tBHP and CSC in epithelial cells and fibroblasts indicates Nfr2 pathway activation. SIGNIFICANCE: This study advances our knowledge of the molecular and cellular mechanisms of cell-specific antioxidant response upon exposure to oxidative stress. Additionally, our observations imply that the eosinophils' distinct biological response may be utilized for endotype-based cell-targeted antioxidant therapy.


Assuntos
Antioxidantes , Oxidantes , Humanos , Antioxidantes/metabolismo , Oxidantes/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular
7.
Eur J Pharmacol ; 941: 175503, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36641100

RESUMO

Cervical and endometrial cancers are among the most dangerous gynaecological malignancies, with high fatality and recurrence rates due to frequent diagnosis at an advanced stage and chemoresistance onset. The NRF2/KEAP1 signalling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. NRF2, activated by ROS, induces the expression of antioxidant enzymes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase which neutralize ROS, protecting cells against oxidative stress damage. However, activation of NRF2/KEAP1 signalling in cancer cells results in chemoresistance, inactivating drug-mediated oxidative stress and protecting cancer cells from drug-induced cell death. We review the literature on the role of the NRF2/KEAP1 pathway in cervical and endometrial cancers, with a focus on the expression of its components and downstream genes. We also examine the role of the NRF2/KEAP1 pathway in chemotherapy resistance and how this pathway can be modulated by natural and synthetic modulators.


Assuntos
Neoplasias do Endométrio , Fator 2 Relacionado a NF-E2 , Humanos , Feminino , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estresse Oxidativo/fisiologia , Neoplasias do Endométrio/tratamento farmacológico
8.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675091

RESUMO

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. With aging and the accumulated effects of environmental stress, retinal pigment epithelial (RPE) cells are particularly susceptible to oxidative damage, which can lead to retinal degeneration. However, the underlying molecular mechanisms of how RPE responds and progresses under oxidative damage are still largely unknown. Here, we reveal that exogenous oxidative stress led to ferroptosis characterized by Fe2+ accumulation and lipid peroxidation in RPE cells. Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1), as a component of the unfolded protein response (UPR) pathway, plays a pivotal role in oxidative-stress-induced cell ferroptosis via the regulation of glutathione depletion. These results indicate the biological significance of Chac1 as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.


Assuntos
Ferroptose , Degeneração Macular , Estresse Oxidativo , Epitélio Pigmentado da Retina , Idoso , Humanos , Células Epiteliais/metabolismo , Ferroptose/genética , Ferroptose/fisiologia , Glutationa/metabolismo , Degeneração Macular/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Epitélio Pigmentado da Retina/metabolismo , Pigmentos da Retina/metabolismo
9.
Life Sci ; 313: 121134, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36544300

RESUMO

AIMS: Hypertension a multifactorial consequence of environmental factors, life style and genetics is the well-recognized risk factor contributing to coronary heart diseases. The antioxidant imbalance, excessive reactive oxygen species (ROS) leads to oxidative stress which is pivotal in progression of hypertension. The present study aims to understand the complex interaction between oxidative stress, inflammation and antioxidant system which is crucial to maintain cellular homeostasis which further can exaggerate hypertension pathophysiology. MATERIALS AND METHODS: The metabolic profile of hypertensive and normotensive subjects from Malwa region, Punjab was compared by estimating lipid profile, cardiac, hepatic and renal markers. The oxidative stress markers (protein carbonyls and lipid peroxidation), inflammatory markers (Nitric oxide, Myeloperoxidase and advanced oxygen protein products), and antioxidant enzymes (Superoxide Dismutase, Catalase, and Total Antioxidant Capacity) were analyzed. KEY FINDINGS: It is observed that the metabolic markers are altered in hypertensive subjects which further these subjects showed increased oxidative, inflammatory profile and compromised antioxidant status when compared with normotensive subjects. Co-relation analysis validated the involvement of inflammation and oxidative stress in impaired endothelial function and vital organ damage. SIGNIFICANCE OF STUDY: These markers may act as early indicators of hypertension which usually do not show any physical symptoms, thus can be diagnosed and treated at the earliest. The current study suggests that disturbed homeostasis, a consequence of altered interaction between antioxidant system and inflammatory events raises the oxidative stress levels which eventually leads to hypertension and associated complications. These indicators can serve as early indicators of future chronic complications of hypertension.


Assuntos
Antioxidantes , Hipertensão , Humanos , Antioxidantes/metabolismo , Estudos Transversais , Prevalência , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo , Inflamação , Peroxidação de Lipídeos
10.
Brain Res ; 1798: 148155, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343723

RESUMO

Interferon-regulatory factor 5 (IRF5) participates in the regulation of apoptosis, affects the phenotype of inflammatory macrophages and plays an essential role in the inflammatory response. However, the role of IRF5 in the progression of amyotrophic lateral sclerosis (ALS) remains largely unknown. Here, we show that IRF5 mainly accumulated in the nucleus in cells expressing the truncated 25 kD C-terminal fragments of TDP-43 (TDP-25, named TDP-25 cells hereafter). IRF5 knockdown using a lentivirus carrying an shRNA in TDP-25 cells exerted a protective effect and reduced the level of the apoptosis-related protein cleaved caspase-9 and the cell cycle arrest protein p21, while increasing the expression of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its target molecule glutamate-cysteine ligase modulatory subunit (GCLM). Furthermore, IRF5-knockdown cells showed improved mitochondrial swelling and cristae dilation. In addition, we found that IRF5 mediated neuronal injury partly through the negative regulation of TANK-binding kinase 1 (TBK1). These data indicate that the loss of IRF5 in TDP-25 cells exerts a protective effect mainly by inhibiting apoptosis, regulating cell cycle arrest and alleviating oxidative stress.


Assuntos
Esclerose Amiotrófica Lateral , Humanos , Esclerose Amiotrófica Lateral/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Estresse Oxidativo/fisiologia , Proteínas de Ciclo Celular/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Fragmentos de Peptídeos/metabolismo
11.
Methods Mol Biol ; 2609: 213-226, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36515838

RESUMO

Transient receptor potential melastatin-2 (TRPM2) is an emerging chemotherapeutic target due to its involvement in poly(ADP-ribose) metabolism and the ability to induce anticancer effects after antagonism of its functions. Normally functioning as a nonspecific cation channel that is activated by free ADP-ribose, TRPM2 is involved with many cellular processes, including the induction of cell death after oxidative stress. What is becoming clear is that antagonism of TRPM2 selectively induces anticancer effects in several types of cancer. We previously demonstrated decreased growth and proliferation, increased levels of DNA damage, and the selective induction of cell death in breast cancer and melanoma cells. Due to these effects, it appears that TRPM2 has a novel role in cancer cells. Further, this novel role appears to involve nuclear function, because our studies, as well as those from other independent groups, demonstrate a nuclear localization of TRPM2 in various types of cancers. Thus, as an emerging therapeutic target, it is important to describe research techniques that can be utilized to analyze TRPM2 function, determine its effects in cancerous and noncancerous cells, and provide molecular biological methods to inhibit or downregulate its function.


Assuntos
Adenosina Difosfato Ribose , Canais de Cátion TRPM , Adenosina Difosfato Ribose/metabolismo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Morte Celular , Estresse Oxidativo/fisiologia , Cátions/metabolismo , Cálcio/metabolismo
12.
Asian J Psychiatr ; 79: 103400, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521406

RESUMO

BACKGROUND: Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). METHOD: We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)- 1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P < 0.05). Significant differences in the activities of CAT (F = 6.068, P = 0.016) and IL-6 levels (F = 6.876, P = 0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r = 0.485, P = 0.006) and between CAT activity and PANSS total scores (r = 0.409, P = 0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r = 0.292, P = 0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r = 0.287, P = 0.014). CONCLUSION: This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.


Assuntos
Esquizofrenia , Masculino , Humanos , Catalase/metabolismo , Interleucina-6 , Estresse Oxidativo/fisiologia , Citocinas/metabolismo , Superóxido Dismutase/metabolismo
13.
Environ Res ; 216(Pt 1): 114391, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36154861

RESUMO

The Eastern Amazon is rich in bauxite ore. The extraction and processing of bauxite lead to the mobilization of Aluminum (Al) and other metals in environmental. We evaluated the metals (Al, Mn, Ba, and Cr) concentration in tissue, water, and sediment associated with antioxidant and oxidative damage responses in Bryconops caudomaculatus. The samplings were done in two hydrological periods (post-rain and post-dry periods) and at three points, located at two rivers: one in the surroundings of the mining area (P1) and other inside the mining area, upstream (P2), and downstream (P3). Defense antioxidant system biomarkers analyzed were total antioxidant capacity (ACAP) and glutathione-S-transferase (GST) activity. As an oxidative damage biomarker, the lipoperoxidation (LPO) was evaluated. Metals concentrations in the water and sediment were higher in the post-rain period compared to post-dry period. The water samples were acidic, with dissolved Al concentrations above the values established by local legislation at all points. In the gills, the metals accumulation was higher in fish from in the surrounding and upstream sites, and in the liver, was higher in fish from downstream site. Fish from the surrounding had increased antioxidant defenses, with higher ACAP in all tissues and higher GST in the gills. Consequently, they had lower levels of LPO. Fish from the mining area had decreased antioxidant defenses, with lower ACAP in all tissues and lower GST in the gills. Consequently, they had higher levels of LPO, indicating oxidative stress. The fish muscle was not responsive to GST and LPO at all sites. We conclude that the oxidative stress observed in the gills and liver of B. caudomaculatus from the area modified by the mining activity reflected the local anthropogenic impact status.


Assuntos
Caraciformes , Poluentes Químicos da Água , Animais , Caraciformes/metabolismo , Antioxidantes/metabolismo , Peroxidação de Lipídeos , Óxido de Alumínio , Estresse Oxidativo/fisiologia , Brânquias/metabolismo , Metais/toxicidade , Metais/metabolismo , Biomarcadores/metabolismo , Fígado/química , Água , Poluentes Químicos da Água/análise , Glutationa Transferase/metabolismo
14.
Environ Res ; 216(Pt 1): 114334, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36162475

RESUMO

Temperature can be considered as pro-oxidant factor that favor the generation of ROS on the species with lower antioxidant efficiency may leads to affect the level of tolerance. So the basic antioxidant enzyme activity (LPO, CAT, SOD, GPx and GST) of gastropod Nerita oryzarum was evaluated at six stations which located between the thermal effluent discharges points from Tarapur Atomic Power Station, India. The antioxidant enzyme activity was shown that all enzyme at discharge point (SII station) where the maximum temperature of heated effluent released. The average maximum values of enzyme activity recorded for LPO, CAT, SOD, GPx and GST were 1.88 ± 0.12, 1.52 ± 0.14, 22.57 ± 0.89, 1.98 ± 0.2 and 17.22 ± 0.63 respectively. The results were inferred the level water temperature directly proportional to the oxidative stress by ROS generation in Nerita oryzarum. Similar results were observed at laboratory experiment under the condition i.e., Treatment 1 (300C), Treatment 2 (350C), Treatment 3 (400C) and Control (250C). The present prima facie work clearly indicated the physiological response of N. oryzarum with respect to antioxidant enzyme activity against the heated effluent released, which will be useful as baseline information for future research work.


Assuntos
Antioxidantes , Gastrópodes , Animais , Antioxidantes/metabolismo , Gastrópodes/metabolismo , Temperatura , Espécies Reativas de Oxigênio , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo , Centrais Elétricas , Catalase/metabolismo
15.
Hear Res ; 427: 108659, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36493529

RESUMO

Hearing loss is the third most prevalent chronic health condition affecting older adults. Age-related hearing loss affects one in three adults over 65 years of age and is caused by both extrinsic and intrinsic factors, including genetics, aging, and exposure to noise and toxins. All cells possess antioxidant defense systems that play an important role in protecting cells against these factors. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) serves as a co-factor for antioxidant enzymes such as glutathione reductase and thioredoxin reductase and is produced by glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase 1 (IDH1) or malic enzyme 1 in the cytosol, while in the mitochondria, NADPH is generated from mitochondrial transhydrogenase, glutamate dehydrogenase, malic enzyme 3 or IDH2. There are three isoforms of IDH: cytosolic IDH1, and mitochondrial IDH2 and IDH3. Of these, IDH2 is thought to be the major supplier of NADPH to the mitochondrial antioxidant defense system. The NADP+/NADPH and NAD+/NADH couples are essential for maintaining a large array of biological processes, including cellular redox state, and energy metabolism, mitochondrial function. A growing body of evidence indicates that mitochondrial dysfunction contributes to age-related structural or functional changes of cochlear sensory hair cells and neurons, leading to hearing impairments. In this review, we describe the current understanding of the roles of NADPH and IDHs in cochlear mitochondrial antioxidant defense and aging.


Assuntos
Isocitrato Desidrogenase , Mitocôndrias , NADP , Estresse Oxidativo , Idoso , Humanos , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Antioxidantes/metabolismo , Perda Auditiva/genética , Perda Auditiva/metabolismo , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Mitocôndrias/metabolismo , NADP/metabolismo , Cóclea/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia
16.
Int J Mol Sci ; 23(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36555492

RESUMO

Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. However, a growing body of evidence suggests that S-glutathionylation plays a key role in core cell processes, particularly in mitochondria, which are the main source of reactive oxygen species. S-nitrosylation, another post-translational modification, was identified >150 years ago, but it was re-introduced as a prototype cell-signaling mechanism only recently, one that tightly regulates core processes within the cell's sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis. In many neurodegenerative disorders, mitochondria dysfunction and oxidative/nitrosative stresses trigger or exacerbate their pathologies. Despite the substantial amount of research for most of these disorders, there are no successful treatments, while antioxidant supplementation failed in the majority of clinical trials. Herein, we discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and Friedreich's ataxia.


Assuntos
Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/metabolismo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Oxirredução , Proteínas/metabolismo , Homeostase
17.
Physiol Rep ; 10(24): e15538, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36541251

RESUMO

Oxidative stress has an important role in brain aging and its consequences include cognitive decline and physiological disorders. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been suggested to decrease oxidative stress. In the current research, the effect of PPARγ activation by pioglitazone(Pio) on learning, memory and oxidative stress was evaluated in aged rats. The rats were divided into five groups. In the Control group, vehicle (saline-diluted dimethyl sulfoxide (DMSO)) and saline were injected instead of Pio and scopolamine (Sco), respectively. In the Sco group, the vehicle was injected instead of Pio and the rats were injected by Sco 30 min before the behavioral tests. In the Sco-Pio 10, Sco-Pio 20, and Sco-Pio 30 groups, 10, 20, and 30 mg/kg Pio was injected and finally, the rats were injected with Sco 30 min before the behavioral tests. Morris water mater maze(MWM) and passive avoidance(PA) tests were carried out, and finally, the hippocampus and cortex were removed for biochemical assessments. The results showed that the highest dose of Pio decreased the traveling time and distance during 5 days of learning and increased the time and distance in the target area on the probe day of MWM. The highest dose of Pio also prolonged the delay time for entering the dark and total time spent in the light while decreasing the total time spent in and the number of entries into the dark in PA test. Pio especially, in the medium and highest doses, decreased MDA while increasing thiol, superoxide dismutase, and catalase in the hippocampus and cortex. It is concluded that PPARγ activation by Pio as an agonist improved learning and memory in aged rats probably by attenuating oxidative stress in the hippocampus and cortex.


Assuntos
Estresse Oxidativo , PPAR gama , Ratos , Animais , PPAR gama/metabolismo , Aprendizagem em Labirinto/fisiologia , Pioglitazona/farmacologia , Estresse Oxidativo/fisiologia , Hipocampo
18.
Biomed Res Int ; 2022: 7497816, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36567907

RESUMO

Background: A plethora of inflammatory, angiogenic, and tissue remodeling factors has been reported in idiopathic epiretinal membranes (ERMs). Herein we focused on the expression of a few mediators (oxidative, inflammatory, and angiogenic/vascular factors) by means of short-term vitreal cell cultures and biomolecular analysis. Methods: Thirty-nine (39) ERMs and vitreal samples were collected at the time of vitreoretinal surgery and biomolecular analyses were performed in clear vitreous, vitreal cell pellets, and ERMs. ROS products and iNOS were investigated in adherent vitreal cells and/or ERMs, and iNOS, VEGF, Ang-2, IFNγ, IL18, and IL22 were quantified in vitreous (ELISA/Ella, IF/WB); transcripts specific for iNOS, p65NFkB, KEAP1, NRF2, and NOX1/NOX4 were detected in ERMs (PCR). Biomolecular changes were analyzed and correlated with disease severity. Results: The higher ROS production was observed in vitreal cells at stage 4, and iNOS was found in ERMs and increased in the vitreous as early as at stage 3. Both iNOS and NOX4 were upregulated at all stages, while p65NFkB was increased at stage 3. iNOS and NOX1 were positively and inversely related with p65NFkB. While NOX4 transcripts were always upregulated, NRF2 was upregulated at stage 3 and inverted at stage 4. No significant changes occurred in the release of angiogenic (VEGF, Ang-2) and proinflammatory (IL18, IL22 and IFNγ) mediators between all stages investigated. Conclusions: ROS production was strictly associated with iNOS and NOX4 overexpression and increased depending on ERM stadiation. The higher iNOS expression occurred as early as stage 3, with respect to p65NFkB and NRF2. These last mediators might have potential prognostic values in ERMs as representative of an underneath retinal damage.


Assuntos
Membrana Epirretiniana , Estresse Oxidativo , Espécies Reativas de Oxigênio , Humanos , Membrana Epirretiniana/genética , Membrana Epirretiniana/metabolismo , Interleucina-18/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia
19.
Molecules ; 27(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36500494

RESUMO

Multiple sclerosis (MS) is a complex neurodegenerative disease. Although its pathogenesis is rather vague in some aspects, it is well known to be an inflammatory process characterized by inflammatory cytokine release and oxidative burden, resulting in demyelination and reduced remyelination and axonal survival together with microglial activation. Antioxidant compounds are gaining interest towards the manipulation of MS, since they offer, in most of the cases, many benefits, due to their pleiotropical activity, that mainly derives from the oxidative stress decrease. This review analyzes research articles, of the last decade, which describe biological in vitro, in vivo and clinical evaluation of various categories of the most therapeutically applied natural antioxidant compounds, and some of their derivatives, with anti-MS activity. It also summarizes some of the main characteristics of MS and the role the reactive oxygen and nitrogen species may have in its progression, as well as their relation with the other mechanistic aspects of the disease, in order for the multi-targeting potential of those antioxidants to be defined and the source of origination of such activity explained. Antioxidant compounds with specific characteristics are expected to affect positively some aspects of the disease, and their potential may render them as effective candidates for neurological impairment reduction in combination with the MS treatment regimen. However, more studies are needed in order such antioxidants to be established as recommended treatment to MS patients.


Assuntos
Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Doenças Neurodegenerativas/tratamento farmacológico , Estresse Oxidativo/fisiologia , Oxirredução
20.
Med Oncol ; 40(1): 12, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352310

RESUMO

Cellular ROS production participates in various cellular functions but its accumulation decides the cell fate. Malignant cells have higher levels of ROS and active antioxidant machinery, a characteristic hallmark of cancer with an outcome of activation of stress-induced pathways like autophagy. Autophagy is an intracellular catabolic process that produces alternative raw materials to meet the energy demand of cells and is influenced by the cellular redox state thus playing a definite role in cancer cell fate. Since damaged mitochondria are the main source of ROS in the cell, however, cancer cells remove them by upregulating the process of mitophagy which is known to play a decisive role in tumorigenesis and tumor progression. Chemotherapy exploits cell machinery which results in the accumulation of toxic levels of ROS in cells resulting in cell death by activating either of the pathways like apoptosis, necrosis, ferroptosis or autophagy in them. So understanding these redox and autophagy regulations offers a promising method to design and develop new cancer therapies that can be very effective and durable for years. This review will give a summary of the current therapeutic molecules targeting redox regulation and autophagy for the treatment of cancer. Further, it will highlight various challenges in developing anticancer agents due to autophagy and ROS regulation in the cell and insights into the development of future therapies.


Assuntos
Neoplasias , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Autofagia , Oxirredução , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
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