Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9352 - 9352

Published: May 27, 2023

This review focuses on the multiple and reciprocal relationships that exist between oxidative stress, hyperglycemia diabetes related metabolic disorders. Human metabolism uses most of consumed glucose under aerobic conditions. Oxygen is needed in mitochondria to obtain energy, as well for action microsomal oxidases cytosolic pro-oxidant enzymes. relentlessly generates a certain amount reactive oxygen species (ROS). Although ROS are intracellular signals necessary some physiological processes, their accumulation leads hyperglycemia, progressive resistance insulin. A cellular versus an antioxidant equilibrium would regulate levels, but pro-inflammatory conditions feed back each other relevance interconnections tends increase those Hyperglycemia promotes collateral through protein kinase C, polyols hexosamine routes. In addition, it also facilitates spontaneous auto-oxidation formation advanced glycation end products (AGEs), which turn interact with receptors (RAGE). The mentioned processes undermine structures, finally giving place progressively greater degree stress further alterations, complications. NFκB major transcription factor involved expression mediators, while Nrf2 regulating response. FoxO equilibrium, its role controversial. summarizes key factors linking diverse routes enhanced vice versa, emphasizing desirable balance proteins.

Language: Английский

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Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 4004 - 4004

Published: Feb. 16, 2023

Most chronic inflammatory illnesses include fibrosis as a pathogenic characteristic. Extracellular matrix (ECM) components build up in excess to cause or scarring. The fibrotic process finally results organ malfunction and death if it is severely progressive. Fibrosis affects nearly all tissues of the body. associated with inflammation, metabolic homeostasis, transforming growth factor-β1 (TGF-β1) signaling, where balance between oxidant antioxidant systems appears be key modulator managing these processes. Virtually every system, including lungs, heart, kidney, liver, can affected by fibrosis, which characterized an excessive accumulation connective tissue components. Organ frequently caused remodeling, also linked high morbidity mortality. Up 45% fatalities industrialized world are damage any organ. Long believed persistently progressing irreversible, has now been revealed very dynamic preclinical models clinical studies variety systems. pathways from and/or main topics this review. Furthermore, different organs their effects was discussed. Finally, we highlight many principal mechanisms fibrosis. These could considered promising targets for development potential therapies important human diseases.

Language: Английский

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Modulation of NRF2/KEAP1 Signaling in Preeclampsia

Cells, Journal Year: 2023, Volume and Issue: 12(11), P. 1545 - 1545

Published: June 4, 2023

Placentation is a key and tightly regulated process that ensures the normal development of placenta fetal growth. Preeclampsia (PE) hypertensive pregnancy-related disorder involving about 5–8% all pregnancies clinically characterized by de novo maternal hypertension proteinuria. In addition, PE are also increased oxidative stress inflammation. The NRF2/KEAP1 signaling pathway plays an important role in protecting cells against damage due to reactive oxygen species (ROS) levels. ROS activate NRF2, allowing its binding antioxidant response element (ARE) region present promoter several genes such as heme oxygenase, catalase, glutathione peroxidase superoxide dismutase neutralize ROS, damages. this review, we analyze current literature regarding preeclamptic pregnancies, discussing main cellular modulators pathway. Moreover, discuss natural synthetic compounds can regulate vivo vitro models.

Language: Английский

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The Role of NQO1 in Ovarian Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7839 - 7839

Published: April 25, 2023

Ovarian cancer is one of the most dangerous gynecologic malignancies showing a high fatality rate because late diagnosis and relapse occurrence due to chemoresistance onset. Several researchers reported that oxidative stress plays key role in ovarian occurrence, growth development. The NAD(P)H:quinone oxidoreductase 1 (NQO1) an antioxidant enzyme that, using NADH or NADPH as substrates reduce quinones hydroquinones, avoids formation highly reactive semiquinones, then protecting cells against stress. In this review, we report evidence from literature describing effect NQO1 on onset progression.

Language: Английский

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Role of SLC7A11/xCT in Ovarian Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 587 - 587

Published: Jan. 2, 2024

Ovarian cancer is one of the most dangerous gynecologic cancers worldwide and has a high fatality rate due to diagnosis at an advanced stage disease as well recurrence occurrence chemotherapy resistance. In fact, chemoresistance weakens therapeutic effects, worsening outcome this pathology. Solute Carrier Family 7 Member 11 (SLC7A11, also known xCT) functional subunit Xc− system, anionic L-cystine/L-glutamate antiporter expressed on cell surface. SLC7A11 expression significantly upregulated in several types which it can inhibit ferroptosis favor proliferation, invasion chemoresistance. increased ovarian tissues, suggesting possible role protein target. review, we provide overview current literature regarding new insights modulation evaluate potential

Language: Английский

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NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 376 - 376

Published: Feb. 4, 2023

Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous metabolite that takes part in many key redox reactions. NAD+ biosynthesis and NAD+-consuming enzymes have been attracting markedly increasing interest since they demonstrated to be involved several crucial biological pathways, impacting genes transcription, cellular signaling, cell cycle regulation. As consequence, pathological conditions are associated with an impairment of intracellular levels, directly or indirectly, which include cardiovascular diseases, obesity, neurodegenerative cancer, aging. In this review, we describe the general pathways starting from different precursors, analyzing actual state-of-art administration precursors blocking NAD+-dependent as strategies increase levels counteract decline ageing. Subsequently, focus on disease-related age-related alterations homeostasis endothelium consequent vascular dysfunction, significantly contributes wide group disorders.

Language: Английский

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Role of Natural and Synthetic Compounds in Modulating NRF2/KEAP1 Signaling Pathway in Prostate Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 3037 - 3037

Published: June 2, 2023

Prostate cancer is the second most common in men worldwide. can be treated by surgery or active surveillance when early diagnosed but, at an advanced metastatic stage, radiation therapy androgen-deprivation needed to reduce progression. However, both of these therapies cause prostate resistance treatment. Several studies demonstrated that oxidative stress involved occurrence, development, progression and treatment resistance. The nuclear factor erythroid 2-related 2 (NRF2)/KEAP1 (Kelch-Like ECH-Associated Protein 1) pathway plays important role protecting cells against damage. Reactive oxygen species (ROS) levels NRF2 activation determine cell fate. In particular, toxic ROS lead physiological death tumor suppression, while lower are associated with carcinogenesis On contrary, a high level promotes survival related activating adaptive antioxidant response. this review, we analyzed current literature regarding natural synthetic compounds modulating NRF2/KEAP1 signaling cancer.

Language: Английский

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Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116432 - 116432

Published: March 22, 2024

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing crucial role the early and sustained phases of DNA damage genomic epigenetic instability, both which are intricately linked to development tumors. The molecular pathways contributing carcinogenesis this context, particularly those related double-strand single-strand breaks DNA, serve as indicators due cancer cases, well factors instability through ectopic expressions. has been considered therapeutic target for many years, an increasing number studies have highlighted promising effectiveness natural products treatment. In regard, we present significant research on targeting oxidative using molecules underscore essential cancer. consequences stress, especially also offer prospects. use epi-drugs capable modulating reorganizing network is beginning emerge remarkably. review, emphasize close connections between tumor transformation, while highlighting substances antioxidants anti-tumoral context.

Language: Английский

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Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1270 - 1270

Published: Oct. 18, 2024

Periodontitis affects up to 40% of adults over 60 years old and is a consequence gingivitis. characterized by chronic inflammation, periodontal damage, alveolar bone resorption. The nuclear factor erythroid 2-related 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays key role in periodontitis modulating redox balance inflammation the periodontium. However, NRF2 expression decreased gingival tissues patients with while oxidative stress significantly increased this pathology. Oxidative lipopolysaccharide (LPS) produced gram-negative bacteria favor production inflammatory causing favoring bone. In review, we analyzed current literature regarding natural synthetic compounds NRF2/KEAP1 vitro vivo models order evaluate new potential treatments that can improve outcome disease.

Language: Английский

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Cellular Modulators of the NRF2/KEAP1 Signaling Pathway in Prostate Cancer

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(7)

Published: July 21, 2023

Prostate cancer is the second most common malignancy in men worldwide. can be treated by surgery, radiotherapy and hormone therapy. The latter, form of androgen-deprivation therapy needed to reduce prostate progression at an advanced stage. Several studies demonstrated that oxidative stress involved occurrence, development Nuclear factor erythroid 2-related 2 (NRF2)/Kelch Like ECH Associated Protein 1 (KEAP1) pathway affected reactive oxygen species (ROS). Furthermore, NRF2/KEAP1 signaling has been investigated several related anti-androgen therapy, biochemical recurrence radiotherapy. In this review we analysed current literature regarding indirect modulators regulation their role as possible therapeutic targets cells.

Language: Английский

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