Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease

Antioxidants, Год журнала: 2024, Номер 13(4), С. 455 - 455

Опубликована: Апрель 12, 2024

Diabetic kidney disease (DKD) is the principal culprit behind chronic (CKD), ultimately developing end-stage renal (ESRD) and necessitating costly dialysis or transplantation. The limited therapeutic efficiency among individuals with DKD a result of our finite understanding its pathogenesis. complex interactions between various factors. Oxidative stress fundamental factor that can establish link hyperglycemia vascular complications frequently encountered in diabetes, particularly DKD. It crucial to recognize essential integral role oxidative development diabetic complications, Hyperglycemia primary trigger an upsurge production reactive oxygen species (ROS), sparking stress. main endogenous sources ROS include mitochondrial production, NADPH oxidases (Nox), uncoupled endothelial nitric oxide synthase (eNOS), xanthine oxidase (XO), cytochrome P450 (CYP450), lipoxygenase. Under persistent high glucose levels, immune cells, complement system, advanced glycation end products (AGEs), protein kinase C (PKC), polyol pathway, hexosamine pathway are activated. Consequently, oxidant–antioxidant balance within body disrupted, which triggers series reactions downstream pathways, including phosphoinositide 3-kinase/protein B (PI3K/Akt), transforming growth beta/p38-mitogen-activated (TGF-β/p38-MAPK), nuclear kappa (NF-κB), adenosine monophosphate-activated (AMPK), Janus kinase/signal transducer activator transcription (JAK/STAT) signaling. might persist even if strict control achieved, be attributed epigenetic modifications. treatment remains unresolved issue. Therefore, reducing intriguing target. clinical trials have shown bardoxolone methyl, erythroid 2-related 2 (Nrf2) activator, blood glucose-lowering drugs, such as sodium-glucose cotransporter inhibitors, glucagon-like peptide-1 receptor agonists effectively slow down progression by Other antioxidants, vitamins, lipoic acid, Nox regulators, present promising option for In this review, we conduct thorough assessment both preclinical studies current findings from focus on targeted interventions aimed at manipulating these pathways. We aim provide comprehensive overview state research area identify key areas future exploration.

Язык: Английский

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Associations of semaglutide with first‐time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real‐world data in the US

Alzheimer s & Dementia, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Abstract INTRODUCTION Emerging preclinical evidence suggests that semaglutide, a glucagon‐like peptide receptor agonist (GLP‐1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration neuroinflammation. However, real‐world its ability to protect Alzheimer's disease (AD) is lacking. METHODS We conducted emulation target trials based on nationwide database of electronic health records (EHRs) 116 million US patients. Seven were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide seven other antidiabetic medications. First‐ever occurred within 3‐year follow‐up period was examined using Cox proportional hazards Kaplan–Meier survival analyses. RESULTS Semaglutide associated significantly reduced risk first‐time diagnosis, most strongly compared insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 0.51]) weakly GLP‐1RAs (HR, 0.59 0.37 0.95]). Similar results seen across obesity status, gender, age groups. DISCUSSION These findings support further studies assess semaglutide's potential in preventing AD. HIGHLIGHTS 40% 70% risks medications, including GLP‐1RAs. lower AD‐related medication prescriptions. reductions Our provide supporting the clinical benefits mitigating initiation development T2DM. delaying or

Язык: Английский

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Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 148 - 148

Опубликована: Янв. 23, 2025

Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of cannabinoid 1 (CB1) receptor, part endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in murine model dextran sodium sulphate (DSS)-induced Methods: Acute was induced 4% DSS 7 days, followed by 3 days water. Chronic modelled over 24 alternating concentrations. The combination 2.5 mg/kg 20 10 evaluated. Key markers were assessed determine efficacy safety, including activity index (DAI), inflammation, cytokine levels, GLP-1, organ health. Results: DSS-induced resulted increased DAI scores, cytokines, inflammation dysregulation GLP-1 ammonia. at significantly improved but ineffective 5 mg/kg. alone showed transient effects. However, either alleviated markers, restored colon integrity reestablished homeostasis. also maintained favourable haematological biochemical profiles, notable reduction colitis-induced elevated ammonia levels. Conclusions: demonstrates synergistic potential low-dose combined as novel, effective safer therapeutic strategy ulcerative

Язык: Английский

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Mechanisms of GLP-1 receptor agonist-induced weight loss: A review of central and peripheral pathways in appetite and energy regulation

The American Journal of Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Апрель 29, 2024

Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing prevalence obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide liraglutide, designed for mellitus treatment, have been explored drugs the treatment obesity. This minireview describes molecular mechanisms liraglutide different metabolic pathways, its mechanism action processes appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, lipid metabolism. Finally, several clinical trial outcomes are described to show safety efficacy these management.

Язык: Английский

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Real-World Evidence Assessment of the Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide

Journal of Diabetes Science and Technology, Год журнала: 2024, Номер 18(6), С. 1517 - 1518

Опубликована: Июль 30, 2024

Язык: Английский

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Glucagon-like peptide 1 agonist and effects on reward behaviour: A systematic review

Physiology & Behavior, Год журнала: 2024, Номер 283, С. 114622 - 114622

Опубликована: Июнь 28, 2024

The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside regulation. There is a growing interest repurposing receptor agonists (GLP-1RAs) as therapeutics for motivation and reward-related behavioural disturbances. Herein, we aim to systematically review the extant evidence on potential effects GLP-1RAs reward system.

Язык: Английский

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Therapeutic Potential of Glucagon-like Peptide-1 Receptor Agonists in Obstructive Sleep Apnea Syndrome Management: A Narrative Review

Diseases, Год журнала: 2024, Номер 12(9), С. 224 - 224

Опубликована: Сен. 23, 2024

Obstructive Sleep Apnea (OSA) is a prevalent disorder characterized by repetitive upper airway obstructions during sleep, leading to intermittent hypoxia and sleep fragmentation. Current treatments, particularly Continuous Positive Airway Pressure (CPAP), face adherence challenges, necessitating novel therapeutic approaches.

Язык: Английский

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Dose-dependent pancreatitis risk associated with GLP-1 agonists

Journal of Diabetes & Metabolic Disorders, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 2, 2025

Язык: Английский

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Impact of GLP‐1 Receptor Agonists on Alcohol‐Related Liver Disease Development and Progression in Alcohol Use Disorder

Alimentary Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in reducing alcohol consumption, but their impact on clinical outcomes patients with use disorder (AUD) remains unclear. We investigated the association between GLP-1RAs and development progression of alcohol-related liver disease (ArLD) AUD. Using TriNetX Research Network, we conducted two retrospective cohort studies comparing versus dipeptidyl peptidase-4 inhibitors (DPP-4is) type 2 diabetes. The first included AUD without ArLD (n = 7132 after propensity score matching), while second comprised established 1896 matching). Primary were incident hepatic decompensation cohort. In (median follow-up: 63.2 months), GLP-1RA users showed significantly lower risks developing compared to DPP-4i (incidence rate: 6.0 vs. 8.7 per 1000 person-years; HR: 0.62, 95% CI: 0.44-0.87, p 0.006). also associated reduced all-cause mortality (HR: 0.53, < 0.001). 28.2 demonstrated 39.5 51.4 0.66, 0.51-0.85, 0.001) users. progressing AUD, suggesting potential therapeutic benefits this population.

Язык: Английский

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