Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(10), P. 2499 - 2574

Published: Aug. 19, 2023

Abstract A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” characterized by low to mild levels oxidants involved in the regulation various biochemical transformations such carboxylation, hydroxylation, peroxidation, modulation signal transduction pathways Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related 2 (Nrf2) other processes. Increased ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result a harmful condition stress (“bad stress”). Although it widely accepted, that many chronic diseases are multifactorial origin, they share common denominator. Here we review importance mechanisms through which contributes pathological states an organism. Attention focused on chemistry ROS RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl nitric oxide, peroxynitrite), their role damage DNA, proteins, membrane lipids. Quantitative qualitative assessment biomarkers also discussed. Oxidative pathology cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s Parkinson’s Down syndrome), psychiatric (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, cancer), aging. The concerted action antioxidants ameliorate effect achieved antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), small molecular weight (vitamins C E, flavonoids, carotenoids, melatonin, ergothioneine, others). Perhaps one most effective vitamin first line defense against peroxidation promising approach appears be use flavonoids), showing weak prooxidant properties may boost cellular systems thus act preventive anticancer agents. Redox metal-based enzyme mimetic compounds potential pharmaceutical interventions sirtuins therapeutic targets for age-related anti-aging strategies

Language: Английский

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Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics

Oral Oncology, Journal Year: 2021, Volume and Issue: 121, P. 105451 - 105451

Published: July 28, 2021

Language: Английский

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RAF-MEK-ERK pathway in cancer evolution and treatment

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 85, P. 123 - 154

Published: May 13, 2021

Language: Английский

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ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer

Cells, Journal Year: 2021, Volume and Issue: 10(10), P. 2509 - 2509

Published: Sept. 22, 2021

The RAF/MEK/ERK signaling pathway regulates diverse cellular processes as exemplified by cell proliferation, differentiation, motility, and survival. Activation of ERK1/2 generally promotes its deregulated activity is a hallmark many cancers. Therefore, components regulators the ERK are considered potential therapeutic targets for cancer, inhibitors this pathway, including some MEK BRAF inhibitors, already being used in clinic. Notably, kinases also have pro-apoptotic functions under certain conditions enhanced can cause tumor death. Although repertoire compounds which mediate activation apoptosis expanding, various anti-cancer induce while exerting their anti-proliferative effects, mechanisms underlying ERK1/2-mediated death still vague. Recent studies highlight importance dual-specificity phosphatases (DUSPs) determining pro- versus anti-apoptotic function cancer. In review, we will summarize recent major findings understanding role apoptosis, focusing on mediating ERK-dependent apoptosis. Studies that further define molecular these relevant to be essential harnessing developing effective cancer treatments.

Language: Английский

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MEK inhibitors for the treatment of non-small cell lung cancer

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Jan. 5, 2021

Abstract BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations both genes have been identified non-small cell lung cancer (NSCLC). They lead to proliferation, differentiation, apoptosis of tumor cells by activating RAS/RAF/MEK/ERK To date, agents that target pathway investigated NSCLC patients harboring mutations. MEK inhibitors gained approval for treatment with NSCLC. According reported findings, combination chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase or is highly significant improving clinical efficacy causing delay occurrence drug resistance. This review summarized existing experimental results presented ongoing studies as well. However, further researches need be conducted indicate how we can combine other drugs significantly increase therapeutic effects on cancer.

Language: Английский

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MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers, Journal Year: 2021, Volume and Issue: 13(12), P. 3026 - 3026

Published: June 17, 2021

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic clinical researchers. The activated more than 50% of human cases; however, activating mutations RAS RAF genes are rarely found HCC, which genetic events leading to activation other cancers. This suggests that there an alternative mechanism behind HCC. Here, we will review recent advances understanding cellular molecular mechanisms involved discuss potential therapeutic strategies targeting context

Language: Английский

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Mechanisms for Modulating Anoikis Resistance in Cancer and the Relevance of Metabolic Reprogramming

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: March 29, 2021

The attachment of cells to the extracellular matrix (ECM) is hallmark structure–function stability and well-being. ECM detachment in localized tumors precedes abnormal dissemination tumor culminating metastasis. Programmed cell death (PCD) activated during tumorigenesis clear off ECM-detached through “anoikis.” However, cancer develop several mechanisms for abrogating anoikis, thus promoting their invasiveness Specific factors, such as growth proteins, pH, transcriptional signaling pathways, oxidative stress, have been reported drivers anoikis resistance, enhancing proliferation Recent studies highlighted key contributions metabolic enabling bypass anoikis. Therefore, understanding driving resistance could help counteract progression prevent This review elucidates dynamics employed by impede proliferation, invasion, In addition, authors discussed other intermediates (especially amino acids nucleotides) that are less explored, which be crucial

Language: Английский

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Genetic Basis and Therapies for Vascular Anomalies

Circulation Research, Journal Year: 2021, Volume and Issue: 129(1), P. 155 - 173

Published: June 24, 2021

Vascular and lymphatic malformations represent a challenge for clinicians. The identification of inherited somatic mutations in important signaling pathways, including the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target rapamycin), RAS (rat sarcoma)/RAF (rapidly accelerated fibrosarcoma)/MEK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinases), HGF (hepatocyte growth factor)/c-Met factor receptor), VEGF (vascular endothelial factor) A/VEGFR receptor) 2 cascades has led to evaluation tailored strategies with preexisting cancer drugs that interfere these pathways. era theranostics started treatment vascular anomalies. Registration: URL: https://www.clinicaltrialsregister.eu ; Unique identifier: 2015-001703-32.

Language: Английский

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Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients, Journal Year: 2021, Volume and Issue: 13(2), P. 690 - 690

Published: Feb. 21, 2021

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest GM can influence health host, several factors modify composition, such as diet, drug intake, lifestyle, geographical locations. Gut dysbiosis affect brain immune homeostasis through microbiota-gut-brain axis play key role pathogenesis neurodegenerative diseases, including dementia Alzheimer's disease (AD). relationship between AD is still elusive, but emerging evidence suggests it enhance secretion lipopolysaccharides amyloids may disturb intestinal permeability blood-brain barrier. In addition, promote hallmarks AD, oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, ultimately causation neural death. Poor dietary habits aging, along with inflammatory responses due to dysbiosis, contribute AD. Thus, modulation probiotics, or fecal transplantation could represent potential therapeutics this review, we discuss therapeutic strategies modulate

Language: Английский

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TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

International Journal of Molecular Medicine, Journal Year: 2021, Volume and Issue: 48(1)

Published: May 18, 2021

Idiopathic pulmonary fibrosis (IPF) is a worldwide disease characterized by the chronic and irreversible decline of lung function. Currently, there no drug to successfully treat except for transplantation. Numerous studies have been devoted study fibrotic process IPF findings showed that transforming growth factor‑β1 (TGF‑β1) plays central role in development IPF. TGF‑β1 promotes through various signaling pathways, including Smad, MAPK, ERK pathways. There are intersections between these which provide new targets researchers drugs. In addition, can affect affecting oxidative stress, epigenetics other aspects. Most processes involved promote IPF, but also inhibit it. This review discusses

Language: Английский

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