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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Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging

Oncotarget, Journal Year: 2018, Volume and Issue: 9(24), P. 17181 - 17198

Published: March 30, 2018

// Carolina Simioni 1 , Giorgio Zauli Alberto M. Martelli 2 Marco Vitale 3, 4 Gianni Sacchetti 5 Arianna Gonelli and Luca Neri Department of Morphology, Surgery Experimental Medicine, University Ferrara, Italy Biomedical Neuromotor Sciences, Bologna, 3 Medicine Surgery, Parma, CoreLab, Azienda Ospedaliero-Universitaria di Life Sciences Biotechnology, Pharmaceutical Biology Laboratory, Correspondence to: Neri, email: [email protected] Keywords: exercise training; nutraceuticals; flavonoids intake; aging; antioxidant supplementation Received: January 26, 2018      Accepted: March 08, Published: 30, 2018 ABSTRACT Physical is considered to be one the beneficial factors a proper lifestyle nowadays seen as an indispensable element for good health, able lower risk disorders cardiovascular, endocrine osteomuscular apparatus, immune system diseases onset potential neoplasms. A moderate programmed physical has often been reported therapeutic both in adulthood aging, since capable promote fitness. Regular alleviates negative effects caused by free radicals offers many health benefits, including reduced all-cause mortality, sarcopenia skeletal muscle, chronic disease, premature death elderly people. However, performance also known induce oxidative stress, inflammation, muscle fatigue. Many efforts have carried out identify micronutrients natural compounds, nutraceuticals, prevent or attenuate exercise-induced stress inflammation. The aim this review discuss benefits deriving from constant activity intake compounds protect body stress. attention will focused mainly on three antioxidants, which are quercetin, resveratrol curcumin. Their properties described, well their expected increase through years can get favorable activity.

Language: Английский

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Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer’s Disease

Cells, Journal Year: 2019, Volume and Issue: 8(5), P. 488 - 488

Published: May 22, 2019

Alzheimer's disease (AD) is a progressive neurodegenerative characterized by memory loss and multiple cognitive impairments. Several decades of intense research have revealed that cellular changes are implicated in the development progression AD, including mitochondrial damage, synaptic dysfunction, amyloid beta (Aβ) formation accumulation, hyperphosphorylated tau (P-Tau) deregulated microRNAs, neuronal patients with AD. Among these, dysfunction damage early events process. Recent also Aβ P-Tau-induced defective autophagy mitophagy prominent AD pathogenesis. Age-dependent increased levels P-Tau reduced several proteins. In addition, abnormal interactions between (1) fission protein Drp1; (2) (3) PINK1/parkin lead to an inability clear damaged mitochondria other debris from neurons. These occur selectively affected The purpose our article highlight recent developments This summarizes aspects dynamics (increased fusion), biogenesis, ATP, free radicals lipid peroxidation, decreased cytochrome c oxidase (COX) activity calcium dyshomeostasis Our discusses how Drp1, Aβ, can enhance clearance mechanisms.

Language: Английский

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Pathophysiology and treatment of cerebral edema in traumatic brain injury

Neuropharmacology, Journal Year: 2018, Volume and Issue: 145, P. 230 - 246

Published: Aug. 4, 2018

Cerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). CE is a leading cause of in-hospital mortality, occurring >60% patients mass lesions, ∼15% those normal initial computed tomography scans. After treatment lesions severe TBI, an important focus acute neurocritical care evaluating managing the secondary process hypertension. This review focuses on contemporary understanding various pathophysiologic pathways contributing to CE, subsequent description potential targeted therapies. There discussion identified cellular/cytotoxic contributors as well mechanisms that influence blood-brain-barrier (BBB) disruption/vasogenic edema, caveat this distinction may be somewhat artificial since molecular processes these interrelated. While exhaustive all putative contributions beyond scope review, roles some key highlighted, references provided for further details. Potential future targets treating presented based mechanisms. We thus aim provide translational synopsis present strategies targeting after TBI context paradigm shift towards precision medicine. article part Special Issue entitled "Novel Treatments Traumatic Brain Injury".

Language: Английский

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The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 10, 2022

The NLRP3 inflammasome is a multiprotein complex that plays pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs DAMPs, oligomerizes activates caspase-1 which initiates processing release of pro-inflammatory cytokines IL-1β IL-18. most extensively studied to date due its array activators aberrant several diseases. Studies using small molecules biologics targeting pathway have shown positive outcomes treating various disease pathologies blocking chronic inflammation. In this review, we discuss recent advances understanding mechanism, pathology, provide broad review therapeutics discovered target their challenges.

Language: Английский

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Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(4), P. 1061 - 1061

Published: April 8, 2020

Among the major neurodegenerative disorders (NDDs), Alzheimer’s disease (AD) and Parkinson’s (PD), are a huge socioeconomic burden. Over many centuries, people have sought cure for NDDs from natural herbals. Many medicinal plants their secondary metabolites reported with ability to alleviate symptoms of NDDs. The mechanisms identified, through which phytochemicals exert neuroprotective effects potential maintenance neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase monoamine oxidase inhibition neurotrophic activities. This article reviews action some herbal products treatment according molecular targets, as well regional sources (Asia, America Africa). A number studies demonstrated beneficial properties plant extracts or bioactive compounds against Herbal may potentially offer new options patients NDDs, is cheaper culturally suitable alternative conventional therapies millions world age-related

Language: Английский

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The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies

Brain Research, Journal Year: 2019, Volume and Issue: 1725, P. 146476 - 146476

Published: Sept. 24, 2019

Alzheimer's disease constitutes a growing cause of cognitive impairment in aging population. Given that current treatments do not produce the desired therapeutic effects, need for finding alternative biological and pharmacological approaches is critical. Accumulating evidence suggests inflammatory oxidative stress responses as potential causal factors impairments healthy aging. Curcumin has received increased interest due to its unique molecular structure targets antioxidant pathways well (directly) amyloid aggregation; one major hallmarks disease. Therefore, this review summarizes preclinical clinical findings on curcumin enhancer normal Databases used literature searches include PubMed, EMBASE Web Science; addition, clinicaltrials.gov was search studies. Overall, animal research shown very promising results potentiating cognition, both physiologically behaviourally. However, human studies are limited less consistent, complicating their interpretation. These inconsistencies may be related differences methodology included Taking into account measurements important biomarkers, optimal dosages curcumin, food interactions, duration treatment would increase our understanding curcumin's effects cognition. In increasing bioavailability could benefit future research.

Language: Английский

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Applications of Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders

Materials, Journal Year: 2022, Volume and Issue: 15(3), P. 804 - 804

Published: Jan. 21, 2022

The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to existence blood-brain barrier (BBB), a closely spaced network blood vessels endothelial cells that functions prevent entry unwanted substances brain. emergence advancement nanotechnology shows favourable prospects overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties imaging agents have dimensions between 1 100 nm could potentially be used ensure enhanced efficacy, cellular uptake, specific transport, delivery molecules brain, owing their modified physico-chemical features. conjugates medicinal plants, or components known as nano phytomedicine, been gaining significance lately novel neuro-therapeutics natural abundance, promising targeted lesser potential show adverse effects. In present review, application, recent trends combined phytomedicine treatment neurological (ND) compared conventional therapies, addressed. Nanotechnology-based efforts performed bioinformatics early diagnosis well futuristic precision medicine ND also discussed context computational approach.

Language: Английский

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Curcumin’s Nanomedicine Formulations for Therapeutic Application in Neurological Diseases

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(2), P. 430 - 430

Published: Feb. 5, 2020

The brain is the body's control center, so when a disease affects it, outcomes are devastating. Alzheimer's and Parkinson's disease, multiple sclerosis diseases that cause large number of human deaths worldwide. Curcumin has demonstrated beneficial effects on health through several mechanisms such as antioxidant, amyloid β-binding, anti-inflammatory, tau inhibition, metal chelation, neurogenesis activity, synaptogenesis promotion. therapeutic limitation curcumin its bioavailability, to address this problem, new nanoformulations being developed. present review aims summarize general bioactivity in neurological disorders, how functional molecules extracted, different types available.

Language: Английский

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Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

Frontiers in Aging, Journal Year: 2022, Volume and Issue: 3

Published: July 12, 2022

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These have shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of opposite effects, extending lifespan. In humans, levels decline with age, chronic kidney diabetes, Alzheimer's disease other conditions. Low correlate an increase the death rate from all causes. acts either obligate coreceptor fibroblast growth factor 23 (FGF23), or soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced kidneys, but also brain, pancreas tissues. On tubular-cell membranes, it associates FGF receptors to bind FGF23. Produced bones, FGF23 regulates excretion phosphate (phosphaturic effect) vitamin D metabolism. Lack results hyperphosphatemia hypervitaminosis D. With human function often deteriorates, lowering levels. This appears promote age-related pathology. Remarkably, inhibits four pathways that been linked aging various ways: Transforming β (TGF-β), insulin-like 1 (IGF-1), Wnt NF-κB. can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis neoplasia. Furthermore, increases cell-protective antioxidant enzymes through Nrf2 FoxO. accord, preclinical therapy ameliorated renal, cardiovascular, diabetes-related neurodegenerative diseases, well cancer. s-Klotho injection was effective, requires further investigation. Several drugs enhance circulating levels, some cross blood-brain barrier potentially act brain. clinical trials, increased noted renin-angiotensin system inhibitors (losartan, valsartan), statin (fluvastatin), mTOR (rapamycin, everolimus), pentoxifylline. work, antidiabetic (metformin, GLP-1-based, GABA, PPAR-γ agonists) enhanced Klotho. traditional medicines and/or nutraceuticals rodents, including astaxanthin, curcumin, ginseng, ligustilide resveratrol. Notably, exercise sport activity review addresses molecular, physiological therapeutic aspects

Language: Английский

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