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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Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 10, 2023

Abstract Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on single vascular complication are no longer suitable for the long-term management patients with diabetes. Diabetic panvascular disease (DPD) is clinical syndrome in which vessels various sizes, including macrovessels microvessels cardiac, cerebral, renal, ophthalmic, peripheral systems diabetes, develop atherosclerosis as common pathology. Pathological manifestations DPDs usually manifest macrovascular atherosclerosis, well microvascular endothelial function impairment, basement membrane thickening, microthrombosis. Cardiac, microangiopathy coexist microangiopathy, while renal retinal predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, risk-predictive relationships diseases. Aggressive glycemic control combined early comprehensive intervention key prevention treatment. In addition widely recommended metformin, glucagon-like peptide-1 agonist, sodium-glucose cotransporter-2 inhibitors, latest aldose reductase peroxisome proliferator-activated receptor-γ agonizts, glucokinases mitochondrial energy modulators, etc. under active development. proposed obtain more systematic care requires center focusing This would leverage advantages cross-disciplinary approach achieve better integration pathogenesis therapeutic evidence. Such strategy confer benefits promote development DPD discipline.

Language: Английский

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Tailored Hydrogel Delivering Niobium Carbide Boosts ROS‐Scavenging and Antimicrobial Activities for Diabetic Wound Healing

Small, Journal Year: 2022, Volume and Issue: 18(27)

Published: June 9, 2022

Abstract The treatment of diabetic wounds remains challenging due to the excess levels oxidative stress, vulnerability bacterial infection, and persistent inflammation response during healing. development hydrogel wound dressings with ideal anti‐inflammation, antioxidant, anti‐infective properties is an urgent clinical requirement. In present study, injectable thermosensitive niobium carbide (Nb 2 C)‐based C@Gel) antioxidative antimicrobial activity developed promote Nb C@Gel system composed C a PLGA‐PEG‐PLGA triblock copolymer. fabricated nanosheets (NSs) show good biocompatibility in vitro cytotoxicity hemocompatibility assays vivo toxicity assays. experiments that NSs can efficiently eliminate reactive oxygen species (ROS), thus protecting cells from stress damage. Meanwhile, also exhibit near‐infrared (NIR) photothermal against both Staphylococcus aureus Escherichia coli . results demonstrate promotes healing by attenuating ROS levels, reducing damage, eradicating infection under NIR irradiation, accelerating angiogenesis. To summarize, system, its ROS‐scavenging, hemostatic activities, be promising effective strategy for wounds.

Language: Английский

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Thermosensitive Hydrogel Incorporating Prussian Blue Nanoparticles Promotes Diabetic Wound Healing via ROS Scavenging and Mitochondrial Function Restoration

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(12), P. 14059 - 14071

Published: March 17, 2022

Diabetic foot ulcer is a serious complication in diabetes patients, imposing physical and economic burden to patients the healthcare system as whole. Oxidative stress thought be key driver of pathogenesis such ulcers. However, no antioxidant drugs have received clinical approval date, underscoring need for further development medications. Hydrogels can applied directly wound site, wherein they function prevent infection maintain local moisture concentrations, addition serving reservoir delivery range therapeutic compounds with potential expedite healing synergistic manner. Herein, we synthesized Prussian blue nanoparticles (PBNPs) capable efficiently scavenging reactive oxygen species (ROS) owing their ability mimic activity catalase (CAT), peroxidase (POD), superoxide dismutase (SOD). In context vitro oxidative stress, these PBNPs were able protect against cytotoxicity, mitochondria from stress-related damage, restore nuclear factor erythroid 2-related 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activity. To expand on results an vivo context, prepared thermosensitive poly (d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA) hydrogel (PLEL)-based dressing which had been homogenously incorporated, then used this platform controlled PBNP release. The resultant PBNPs@PLEL was improve diabetic healing, decrease ROS production, promote angiogenesis, reduce pro-inflammatory interleukin-6 (IL-6) tumor necrosis factor-α (TNF-α) levels within wounds. Overall, our suggest that holds great promise treatment

Language: Английский

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Pathophysiological Association between Diabetes Mellitus and Endothelial Dysfunction

Antioxidants, Journal Year: 2021, Volume and Issue: 10(8), P. 1306 - 1306

Published: Aug. 18, 2021

Endothelial dysfunction plays a critical role in atherosclerosis progression, leading to cardiovascular complications. There are significant associations between diabetes mellitus, oxidative stress, and endothelial dysfunction. Oxidative stress is increased by chronic hyperglycemia acute glucose fluctuations induced postprandial patients with mellitus. In addition, selective insulin resistance the phosphoinositide 3-kinase/Akt/endothelial nitric oxide (NO) synthase pathway cells involved decreased NO production endothelin-1 from endothelium, resulting clinical setting, selecting an appropriate therapeutic intervention that improves or augments function important for preventing diabetic vascular Hypoglycemic drugs reduce decreasing rise blood levels, such as glinides, α-glucosidase inhibitors dipeptidyl peptidase 4 inhibitors, hypoglycemic ameliorate sensitivity, thiazolidinediones metformin, expected improve augment diabetes. Glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 may through multiple mechanisms, some of which independent control signaling. Oral administration antioxidants not recommended due lack evidence efficacy against

Language: Английский

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Exploring Therapeutic Potential of Catalase: Strategies in Disease Prevention and Management

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 697 - 697

Published: June 14, 2024

The antioxidant defense mechanisms play a critical role in mitigating the deleterious effects of reactive oxygen species (ROS). Catalase stands out as paramount enzymatic antioxidant. It efficiently catalyzes decomposition hydrogen peroxide (H

Language: Английский

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Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 5, 2024

Abstract Diabetic wounds are characterized by incomplete healing and delayed healing, resulting in a considerable global health care burden. Exosomes lipid bilayer structures secreted nearly all cells express characteristic conserved proteins parent cell-associated proteins. harbor diverse range of biologically active macromolecules small molecules that can act as messengers between different cells, triggering functional changes recipient thus endowing the ability to cure various diseases, including diabetic wounds. accelerate wound regulating cellular function, inhibiting oxidative stress damage, suppressing inflammatory response, promoting vascular regeneration, accelerating epithelial facilitating collagen remodeling, reducing scarring. from tissues or potentially possess functions varying levels promote healing. For example, mesenchymal stem cell-derived exosomes (MSC-exos) have favorable potential field due their superior stability, permeability, biocompatibility, immunomodulatory properties. Exosomes, which derived skin components, modulate inflammation regeneration key turn promotes Therefore, this review mainly emphasizes roles mechanisms sources, represented MSCs improving A deeper understanding therapeutic will yield promising candidates perspectives for management.

Language: Английский

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Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 17, 2024

Abstract Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place heavy financial strain on both patients the healthcare establishment. The lack effective treatments contributes to this pessimistic situation negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as most likely new breakthrough advancement in treating diabetes diabetes‐associated complication due capacity intercellular communication, modulating local microenvironment, regulating cellular processes. In present review, we briefly outlined properties MSCs-derived exosomes, provided thorough summary their biological functions potential uses related complications.

Language: Английский

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Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2846 - 2846

Published: March 5, 2022

Oxidative stress is a major component of cell damage and fat, as such, it occupies central position in the pathogenesis metabolic disease. Nuclear factor-erythroid-derived 2-related factor 2 (Nrf2), key transcription that coordinates expression genes encoding antioxidant detoxifying enzymes, regulated primarily by Kelch-like ECH-associated protein 1 (Keap1). However, involvement Keap1–Nrf2 pathway tissue organism homeostasis goes far beyond protection from cellular stress. In this review, we focus on evidence for Nrf2 dysfunction during development several metabolic/inflammatory disorders, including diabetes diabetic complications, obesity, inflammatory bowel disease, autoimmune diseases. We also review beneficial role current molecular agonists summarize their use ongoing clinical trials. conclude promising target regulation numerous diseases associated with oxidative inflammation. more studies are needed to explore safety implications before therapeutic practice.

Language: Английский

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Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis

Cells, Journal Year: 2022, Volume and Issue: 11(20), P. 3229 - 3229

Published: Oct. 14, 2022

Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes adipose-derived (ADSC-EXOs) healing through modulation oxidative stress. We found that ADSC-EXOs proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, endothelial cells. Furthermore, reduced reactive oxygen species (ROS) levels these protected them against hypoxic stress damage. Finally, local injection at sites significantly increased collagen deposition neovascularization while reducing ROS cell death; thus, it led to accelerated closure. The underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on surface; be inhibited an anti-HSP90 antibody. Exosomal HSP90 bind low-density lipoprotein receptor-related 1 (LRP1) receptor recipient membrane, leading activation downstream AKT signaling pathway. Knockdown LRP1 inhibition pathway LY294002 fibroblasts was sufficient impair beneficial effect ADSC-EXOs. In summary, closure exosomal HSP90/LRP1/AKT

Language: Английский

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