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1.
Sci Rep ; 14(1): 8105, 2024 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582792

RESUMO

The response of 14 Hollyhock (Alcea rosea L.) varieties to salinity were evaluated in a field experiment over two growing seasons. Carotenoid, Chl a, Chl b, total Chl, proline and MDA content, CAT, APX and GPX activity and petal and seeds yields were determined in order to investigate the mechanism of salt tolerance exhibited by Hollyhock, and too identify salt tolerant varieties. Overall, the photosynthetic pigment content,petal and seed yields were reduced by salt stress. Whereas the proline and MDA content, and the CAT, APX and GPX activities increased as salt levels increased. However, the values of the measured traits were dependent upon the on the level of salt stress, the Varietie and the interaction between the two variables. Based upon the smallest reduction in petal yield, the Masouleh variety was shown to be the most salt tolerant, when grown under severe salt stress. However, based upon the smallest reduction in seed yield, Khorrmabad was the most tolerant variety to severe salt stress. These data suggest that the selection of more salt tolerant Hollyhock genotypes may be possible based upon the wide variation in tolerance to salinity exhibited by the varieties tested.


Assuntos
Malvaceae , Estresse Oxidativo , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Tolerância ao Sal/genética , Prolina/metabolismo
2.
J Headache Pain ; 25(1): 50, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565987

RESUMO

BACKGROUND: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated. METHODS: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1ß, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C. RESULTS: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2. CONCLUSIONS: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine.


Assuntos
Benzofuranos , Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Camundongos , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Fator 2 Relacionado a NF-E2/uso terapêutico , Doenças Neuroinflamatórias , Espécies Reativas de Oxigênio , Fotofobia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/fisiologia , Nitroglicerina/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/metabolismo
3.
Trends Endocrinol Metab ; 35(2): 125-141, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38577754

RESUMO

Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality.


Assuntos
Dieta Cetogênica , Humanos , Corpos Cetônicos/metabolismo , Jejum , Estresse Oxidativo/fisiologia , Inflamação
4.
Yakugaku Zasshi ; 144(4): 419-429, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38556317

RESUMO

In view of the current claim by many researchers that biological aging is a treatable disease, the possibility is discussed whether the claim is realistic, based on several proposed mechanisms of aging. The definition of biological aging is stated referring to physiological aging and pathological aging, since biological aging must be defined for the discussion of whether it can be cured. Aging in animal model is compared with that in humans in terms of common age-associated phenotypes. Major proposed mechanisms of aging are next examined including Genome Instability Theory of aging, Free Radical or Oxidative Stress Theory of Aging, Mitochondrial Theory of Aging, Error Catastrophe Theory of Aging/Translational Error Theory of Aging, Altered Protein Theory of Aging/Proteostasis Theory of Aging, and Epigenetic Theory of Aging. Finally, we discuss whether treatment of aging as a disease is realistic in comparison with possible lifespan extension by retardation of biological aging.


Assuntos
Envelhecimento , Estresse Oxidativo , Animais , Humanos , Envelhecimento/metabolismo , Estresse Oxidativo/fisiologia , Radicais Livres/metabolismo , Longevidade/genética , Mitocôndrias/metabolismo
5.
Transl Vis Sci Technol ; 13(3): 24, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38546981

RESUMO

Purpose: To investigate the potential effects and mechanism of nicotinamide riboside (NR) on the oxidative stress and fibrosis model of human trabecular meshwork (HTM) cell line cells. Methods: HTM cells were pretreated with NR, followed by the induction of oxidative injury and fibrosis by hydrogen peroxide (H2O2) and TGF-ß2, respectively. Cell viability was tested using Hoechst staining and MTT assays, cell proliferation was assessed by EdU assay, and cell apoptosis was detected by flow cytometry and western blotting. DCFH-DA and DHE probes were used to measure the level of reactive oxygen species (ROS), and MitoTracker staining was used to measure the mitochondrial membrane potential (MMP). Fibrotic responses, including cell migration and deposition of extracellular matrix (ECM) proteins, were detected via Transwell assays, qRT-PCR, and immunoblotting. Results: NR pretreatment improved the viability, proliferation, and MMP of H2O2-treated HTM cells. Compared to cells treated solely with H2O2, HTM cells treated with both NR and H2O2, exhibited a reduced rate of apoptosis and generation of ROS. Compared with H2O2 pretreatment, NR pretreatment upregulated expression of the JAK2/Stat3 pathway but inhibited mitogen-activated protein kinase (MAPK) pathway expression. Moreover, 10-ng/mL TGF-ß2 promoted cell proliferation and migration, which were inhibited by NR pretreatment. Both qRT-PCR and immunoblotting showed that NR inhibited the expression of fibronectin in a TGF-ß2-induced fibrosis model. Conclusions: NR has a protective effect on oxidative stress and fibrosis in HTM cells, which may be related to the JAK2/Stat3 pathway and MAPK pathway. Translational Relevance: Our research provides the ongoing data for potential therapy of NAD+ precursors in glaucoma.


Assuntos
Niacinamida/análogos & derivados , Compostos de Piridínio , Malha Trabecular , Fator de Crescimento Transformador beta2 , Humanos , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Fator de Crescimento Transformador beta2/metabolismo , Fator de Crescimento Transformador beta2/farmacologia , Malha Trabecular/metabolismo , Malha Trabecular/patologia , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo/fisiologia , Fibrose
6.
Neurologia (Engl Ed) ; 39(3): 292-301, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553104

RESUMO

INTRODUCTION: This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune disease. DEVELOPMENT: The oxidative stress concept has been defined by an imbalance between oxidants and antioxidants in favor of the oxidants. There is necessary to do physiological functions, like the respiration chain, but in certain conditions, the production of reactive species overpassed the antioxidant systems, which could cause tissue damage. On the other hand, it is well established that inflammation is a complex reaction in the vascularized connective tissue in response to diverse stimuli. However, an unregulated prolonged inflammatory process also can induce tissue damage. CONCLUSION: Both inflammation and oxidative stress are interrelated since one could promote the other, leading to a toxic feedback system, which contributes to the inflammatory and demyelination process in MS.


Assuntos
Esclerose Múltipla , Humanos , Estresse Oxidativo/fisiologia , Inflamação , Antioxidantes/metabolismo , Oxidantes
7.
Medicine (Baltimore) ; 103(11): e37421, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489713

RESUMO

BACKGROUND: Endometriosis (EMT) a common gynecological condition in women, an inflammatory disease characterized by the presence of endometrial tissue on organs and tissues in the pelvis, and is mainly associated with chronic pelvic pain and infertility. As the etiology has not been fully elucidated, current treatment is limited to surgery, hormones and painkillers, with more side effects and difficulty in achieving long-term relief. Oxidative stress manifests itself as an overproduction of reactive oxygen species, which has an integral impact in the pathology of female reproductive disorders. In this review, we evaluate the mechanisms of iron overload-induced oxidative stress and ferroptosis in EMT and their pathophysiological implications. METHODS: Because the etiology has not been fully elucidated, current treatments are limited to surgery, hormones, and painkillers, which have many side effects and are difficult to achieve long-term relief. RESULTS: We interpreted that antioxidants as well as ferroptosis inducers show promising results in the treatment of EMT, but their application in this population needs to be further investigated. CONCLUSION: In combination with the interpretation of previous studies, it was shown that iron overload is present in the peritoneal fluid, endometriotic lesions, peritoneum and macrophages in the abdominal cavity. However, the programmed cellular ferroptosis associated with iron overload is resisted by endometriotic foci, which is critical to the pathophysiology of EMT with local iron overload and inflammation.


Assuntos
Endometriose , Ferroptose , Sobrecarga de Ferro , Feminino , Humanos , Endometriose/patologia , Estresse Oxidativo/fisiologia , Sobrecarga de Ferro/complicações , Hormônios
8.
Int J Biol Macromol ; 264(Pt 2): 130761, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467213

RESUMO

Diabetic vascular complications include diabetic macroangiopathy and diabetic microangiopathy. Diabetic microangiopathy is characterised by impaired microvascular endothelial function, basement membrane thickening, and microthrombosis, which may promote renal, ocular, cardiac, and peripheral system damage in diabetic patients. Therefore, new preventive and therapeutic strategies are urgently required. Sirt1, a member of the nicotinamide adenine dinucleotide-dependent histone deacetylase class III family, regulates different organ growth and development, oxidative stress, mitochondrial function, metabolism, inflammation, and aging. Sirt1 is downregulated in vascular injury and microangiopathy. Moreover, its expression and distribution in different organs correlate with age and play critical regulatory roles in oxidative stress and inflammation. This review introduces the background of diabetic microangiopathy and the main functions of Sirt1. Then, the relationship between Sirt1 and different diabetic microangiopathies and the regulatory roles mediated by different cells are described. Finally, we summarize the modulators that target Sirt1 to ameliorate diabetic microangiopathy as an essential preventive and therapeutic measure for diabetic microangiopathy. In conclusion, targeting Sirt1 may be a new therapeutic strategy for diabetic microangiopathy.


Assuntos
Diabetes Mellitus , Angiopatias Diabéticas , Humanos , Sirtuína 1/metabolismo , Diabetes Mellitus/metabolismo , Estresse Oxidativo/fisiologia , Inflamação
9.
Neurochem Int ; 175: 105701, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38428503

RESUMO

Brain tissue is highly enriched in lipids, the majority of which are glycerophospholipids. Glycerophospholipids are the major constituents of cellular membranes and play an important role in maintaining integrity and function of cellular and subcellular structures. Any changes in glycerophospholipid homeostasis can adversely affect brain functions. Traumatic brain injury (TBI), an acquired injury caused by the impact of external forces to the brain, triggers activation of secondary biochemical events that include perturbation of lipid homeostasis. Several studies have demonstrated glycerophospholipid dysregulation in the brain and circulation after TBI. This includes spatial and temporal changes in abundance and distribution of glycerophospholipids in the injured brain. This is at least in part mediated by TBI-induced oxidative stress and by activation of lipid metabolism pathways involved in tissue repairing. In this review, we discuss current advances in understanding of the mechanisms and implications of glycerophospholipid dysregulation following TBI.


Assuntos
Lesões Encefálicas Traumáticas , Glicerofosfolipídeos , Humanos , Glicerofosfolipídeos/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo/fisiologia
10.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474191

RESUMO

Mitochondrial dysfunction and metabolic reprogramming have been extensively studied in many disorders ranging from cardiovascular to neurodegenerative disease. Obesity has previously been associated with mitochondrial fragmentation, dysregulated glycolysis, and oxidative phosphorylation, as well as increased reactive oxygen species production. Current treatments focus on reducing cellular stress to restore homeostasis through the use of antioxidants or alterations of mitochondrial dynamics. This review focuses on the role of mitochondrial dysfunction in obesity particularly for those suffering from asthma and examines mitochondrial transfer from mesenchymal stem cells to restore function as a potential therapy. Mitochondrial targeted therapy to restore healthy metabolism may provide a unique approach to alleviate dysregulation in individuals with this unique endotype.


Assuntos
Asma , Doenças Mitocondriais , Doenças Neurodegenerativas , Humanos , Estresse Oxidativo/fisiologia , Obesidade , Doenças Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Int J Mol Sci ; 25(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473944

RESUMO

Oxidative stress (OS) and inflammation are two important and well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence of easily oxidizable polyunsaturated fatty acids and the weak antioxidant defenses, the brain is particularly vulnerable to oxidative injury. Uncertainty exists over whether these deficits contribute to the development of NDDs or are solely a consequence of neuronal degeneration. Furthermore, these two pathological hallmarks are linked, and it is known that OS can affect the inflammatory response. In this review, we will overview the last findings about these two pathways in the principal NDDs. Moreover, we will focus more in depth on amyotrophic lateral sclerosis (ALS) to understand how anti-inflammatory and antioxidants drugs have been used for the treatment of this still incurable motor neuron (MN) disease. Finally, we will analyze the principal past and actual clinical trials and the future perspectives in the study of these two pathological mechanisms.


Assuntos
Esclerose Amiotrófica Lateral , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Esclerose Amiotrófica Lateral/metabolismo , Inflamação/tratamento farmacológico
12.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474158

RESUMO

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.


Assuntos
Cardiopatias , Sepse , Humanos , Estresse Oxidativo/fisiologia , Sepse/metabolismo , Miócitos Cardíacos/metabolismo , Cardiopatias/metabolismo , Estresse Nitrosativo
13.
Vestn Otorinolaringol ; 89(1): 16-20, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38506020

RESUMO

The problem of chronic rhinitis (CR) remains unresolved in the world, while it has a negative impact on the quality of life of patients. Chronic forms of rhinitis suffer from 10-20% of the population, and its symptoms in epidemiological studies are noted in 40% of respondents. One of the leading mechanisms of disease occurrence is oxidative stress. OBJECTIVE: To study the state of the processes of lipid peroxidation and antioxidant protection in various types of chronic rhinitis. MATERIAL AND METHODS: The study included 50 patients with CR, of which 21 were with chronic allergic rhinitis (CALR), 20 with chronic vasomotor rhinitis (CVR), 9 with chronic atrophic rhinitis (CAR). The control group was represented by 50 practically healthy volunteers with no otorhinolaryngological complaints. The indicators of the LPO-AOD system in erythrocytes were evaluated by spectrophotometric methods. Statistical data processing was carried out using the Statistica 7.0 software package (StatSoft, USA). RESULTS: In all patients with CR in the blood erythrocytes, an increase in the level of malondialdehyde (MDA), a decrease in the activity of superoxide dismutase (SOD), catalase (CAT) relative to the control group was found. With CAR, the most pronounced changes are determined, with CVR - minimal. In patients with CR, lipid peroxidation is activated, MDA increases by 1.29 times, by 1.37 times with CAR, and by 1.31 times with CALR relative to normal values. The activity of the antioxidant system decreases, which reflects the classical variant of inhibition of antioxidant enzymes: SOD is reduced by 1.08 times in CAR, by 1.07 times in CALR, and 1.04 times in CVR, CAT in CAR is reduced by 1.02 times; CALR by 1.02 times, with CVR by 1.01 times. The coefficient of oxidative stress with CVR is 1.36, with CAR is 1.5, with CALR is 1.42. CONCLUSION: In CR, the predominance of pro-oxidant processes over antioxidant ones is revealed, a slight oxidative stress is detected, probably due to the presence of hypoxia and intoxication syndrome. An in-depth study of lipid peroxidation processes and factors of the antioxidant defense system, depending on the CR phenotype, can be used to correct therapy and prevent exacerbations, as well as markers of progression and prognosis of chronic rhinitis.


Assuntos
Antioxidantes , Rinite Alérgica , Humanos , Peroxidação de Lipídeos/fisiologia , Qualidade de Vida , Glutationa Peroxidase/metabolismo , Catalase/metabolismo , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo , Rinite Alérgica/diagnóstico , Malondialdeído
14.
Front Cell Infect Microbiol ; 14: 1348713, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510969

RESUMO

Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.


Assuntos
Antioxidantes , Sepse , Animais , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Sepse/tratamento farmacológico , Sepse/metabolismo , Mitocôndrias/metabolismo
15.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542335

RESUMO

Reactive oxygen species (ROS) and free radicals work to maintain homeostasis in the body, but their excessive production causes damage to the organism. The human body is composed of a variety of cells totaling over 60 trillion cells. Each cell performs different functions and has a unique lifespan. The lifespan of cells is preprogrammed in their genes, and the death of cells that have reached the end of their lifespan is called apoptosis. This is contrary to necrosis, which is the premature death of cells brought about by physical or scientific forces. Each species has its own unique lifespan, which in humans is estimated to be up to 120 years. Elucidating the mechanism of the death of a single cell will lead to a better understanding of human death, and, conversely, the death of a single cell will lead to exploring the mechanisms of life. In this sense, research on active oxygen and free radicals, which are implicated in biological disorders and homeostasis, requires an understanding of both the physicochemical as well as the biochemical aspects. Based on the discussion above, it is clear to see that active oxygen and free radicals have dual functions of both injuring and facilitating homeostasis in living organisms.


Assuntos
Antioxidantes , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Radicais Livres/metabolismo , Antioxidantes/metabolismo , Apoptose
16.
Medicine (Baltimore) ; 103(9): e37360, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428906

RESUMO

Oxidative stress, a condition characterized by an imbalance between reactive oxygen species (ROS) production and the body's ability to detoxify them, has emerged as a pivotal factor in the pathophysiology of various diseases. Red blood cells (RBCs), essential components of the circulatory system, are particularly susceptible to oxidative damage due to their high oxygen-carrying capacity and the abundance of vulnerable biomolecules. This review comprehensively explores the intricate mechanisms underlying oxidative stress-induced damage to red blood cells and the subsequent implications for overall health and disease. We delve into the sources of ROS generation within RBCs, including metabolic processes and external factors, shedding light on the delicate redox balance that governs cellular homeostasis. The impact of oxidative stress on red blood cells extends beyond the confines of their primary physiological role, as these cells actively participate in immune responses, inflammation modulation, and nitric oxide metabolism. Consequently, understanding the implications of oxidative stress on RBCs provides valuable insights into the broader landscape of health and disease. In conclusion, this review underscores the critical role of oxidative stress in influencing red blood cell physiology and its far-reaching implications for human health. Elucidating the molecular intricacies of this relationship not only enhances our understanding of fundamental biological processes but also paves the way for the development of targeted therapeutic interventions to mitigate the adverse effects of oxidative stress on red blood cells and, by extension, on overall health.


Assuntos
Eritrócitos , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Oxirredução , Eritrócitos/metabolismo , Suscetibilidade a Doenças
17.
Clin Exp Pharmacol Physiol ; 51(4): e13844, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38350599

RESUMO

Botulinum neurotoxin A (BoNT) is being shown to have anticancer action as a potential adjuvant treatment. The transient receptor potential (TRP) melastatin 2 (TRPM2) stimulator action of BoNT was reported in glioblastoma cells, but not in colorectal cancer (HT29) cells. By activating TRPM2, we evaluated the impacts of BoNT and oxaliplatin (OXA) incubations on oxidant and apoptotic values within the HT29 cells. Control, BoNT (5 IU for 24 h), OXA (50 µM for 24 h) and their combinations were induced. We found that TRPM2 protein is upregulated and mediates enhanced BoNT and OXA-induced Ca2+ entry in cells as compared to control cells. The increase of free reactive oxygen species (ROS), but the decrease of glutathione is the main ROS responsible for TRPM2 activation on H29 exposure to oxidative stress. BoNT and OXA-mediated Ca2+ entry through TRPM2 stimulation in response to H2 O2 results in mitochondrial Ca2+ overload, followed by mitochondrial membrane depolarization, apoptosis and caspase-3/-8/-9, although they were diminished in the TRPM2 antagonist groups (N-(p-amylcinnamoyl)anthranilic acid and carvacrol). In conclusion, by increasing the susceptibility of HT29 tumour cells to oxidative stress and apoptosis, the combined administration of BoNT and OXA via the targeting of TRPM2 may offer a different approach to kill the tumour cells.


Assuntos
Toxinas Botulínicas Tipo A , Neoplasias Colorretais , Canais de Cátion TRPM , Humanos , Oxaliplatina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Toxinas Botulínicas Tipo A/metabolismo , Regulação para Cima , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Morte Celular , Estresse Oxidativo/fisiologia , Apoptose/fisiologia , Neoplasias Colorretais/tratamento farmacológico , Cálcio/metabolismo
18.
Biomolecules ; 14(2)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38397443

RESUMO

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the cellular anti-oxidant defense mechanisms, plays a critical role in the pathogenesis of various human diseases. Redox metabolism, comprising a network of enzymes and genes, serves as a crucial regulator of ROS levels and maintains cellular homeostasis. This review provides an overview of the most important human genes encoding for proteins involved in ROS generation, ROS detoxification, and production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), and the genetic disorders that lead to dysregulation of these vital processes. Insights gained from studies on inherited monogenic metabolic diseases provide valuable basic understanding of redox metabolism and signaling, and they also help to unravel the underlying pathomechanisms that contribute to prevalent chronic disorders like cardiovascular disease, neurodegeneration, and cancer.


Assuntos
Antioxidantes , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Oxirredução , Antioxidantes/metabolismo , Transdução de Sinais
19.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396687

RESUMO

The core pathological event in Parkinson's disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The reasons why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans are still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite the fact that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Dopamina/metabolismo , Substância Negra/metabolismo , Neurônios Dopaminérgicos/metabolismo , Estresse Oxidativo/fisiologia , Metabolismo Energético
20.
Sci Total Environ ; 919: 170670, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325473

RESUMO

Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in various environmental media (i.e., water, soil, and indoor dust) and biological and human samples (i.e., serum and brain). Both epidemiological and animal studies have determined an association between exposure to BPs and an increased risk of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), including cognitive abnormalities and behavioral disturbances. Hence, understanding the biological responses to different BPs is essential for prevention, and treatment. This study provides an overview of the underlying pathogenic molecular mechanisms as a valuable basis for understanding neurodegenerative disease responses to BPs, including accumulation of misfolded proteins, reduction of tyrosine hydroxylase and dopamine, abnormal hormone signaling, neuronal death, oxidative stress, calcium homeostasis, and inflammation. These findings provide new insights into the neurotoxic potential of BPs and ultimately contribute to a comprehensive health risk evaluation.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Humanos , Doenças Neurodegenerativas/induzido quimicamente , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo/fisiologia
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