Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2873 - 2873

Published: March 21, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation and progressive joint destruction. Recent data underscore oxidative stress as primary factor in the pathophysiology of rheumatoid arthritis, intensifying inflammatory processes tissue damage via overproduction reactive oxygen species (ROS) compromised antioxidant defenses. Current therapies, including disease-modifying antirheumatic drugs (DMARDs), primarily target immune dysregulation but fail to address stress, necessitating novel adjunctive treatment strategies. This review explores potential antioxidant-based therapies complementary approaches RA management. Natural compounds such curcumin, resveratrol, sulforaphane, propolis exhibit strong anti-inflammatory antioxidative properties modulating redox-sensitive pathways, nuclear kappa-light-chain-enhancer activated B cells (NF-κB) erythroid 2-related 2(Nrf2)/heme oxygenase (HO-1). N-acetylcysteine (NAC) replenishes intracellular glutathione, enhancing cellular resilience against stress. Additionally, molecular hydrogen (H2) selectively neutralizes harmful ROS, reducing inflammation. The role vitamin supplementation (D, B12, C, K) regulating responses protecting structures also discussed. aims evaluate efficacy clinical applications RA, emphasizing their mitigating improving outcomes. While preliminary findings are promising, further trials needed establish standardized dosing, long-term safety, integration into current protocols.

Language: Английский

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The Role of Xenobiotic Caffeine on Cardiovascular Health: Promises and Challenges

Journal of Xenobiotics, Journal Year: 2025, Volume and Issue: 15(2), P. 51 - 51

Published: March 31, 2025

Cardiovascular diseases (CVDs) represent a leading cause of premature mortality and disability worldwide, with their incidence expected to rise, potentially reaching 24 million deaths per year by 2030. These multifactorial diseases, including hypertension, coronary artery disease, arrhythmia, heart failure, are often linked metabolic disturbances such as diabetes, oxidative stress, endothelial dysfunction, inflammation. Natural compounds, caffeine, have been explored for potential therapeutic effects on CVDs. Caffeine, found in coffee, tea, cocoa, various energy drinks, is widely consumed psychoactive compound noted analgesic anti-inflammatory properties. Despite its long history use, caffeine’s impact cardiovascular health remains controversial, both beneficial harmful reported. This review examines the current literature caffeine (CVDs), an emphasis preclinical clinical studies, pharmacokinetic properties, molecular mechanisms it modulates. There evidence that moderate intake can be some CVDs, while other dyslipidemia, collected so far suggests could detrimental since increases total cholesterol levels. But variability dosage, patterns, individual factors (such genetics diet) complicates reliability results. Additionally, challenges related dose standardization absence consistent trial designs hinder full utilization CVD treatment. Nonetheless, appears safe individuals without significant conditions. Future research should aim well-designed studies precise patient cohorts standardized methodologies better assess role management.

Language: Английский

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Deoxynivalenol exposure-related male reproductive toxicity in mammals: Molecular mechanisms, detoxification and future directions

Environment International, Journal Year: 2025, Volume and Issue: 199, P. 109478 - 109478

Published: April 17, 2025

An increasing body of evidence indicates that exposure to widespread, environmental and food contaminants such as mycotoxins may cause endocrine disorders infertility. Deoxynivalenol (DON), which is a toxic secondary metabolite produced by Fusarium fungi, can lead multiple harmful effects in humans animals, hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, neurotoxicity, genetic toxicity carcinogenicity. Recently, there has been growing concern about DON-induced male Exposure DON its metabolites damage the structure function reproductive organs, resulting impairment gametogenesis thus impaired fertility. Potential molecular mechanisms involve oxidative stress, inflammatory response, mitochondrial dysfunction, apoptosis, cell cycle arrest, pyroptosis, ferroptosis. Moreover, several signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinase, NLR family pyrin domain containing 3, factor erythroid 2-related 2, AMP-activated apoptotic microRNAs are involved these detrimental biological processes. Research shown antioxidants, small-molecule inhibitors, or proteins (such lactoferrin) supplementation potentially offer protective targeting pathways. This review comprehensively summarizes on mammals, underlying emphasizes potential small molecules therapeutics. In further, systematic risk assessment when at doses human health, in-depth precise mechanism investigation using emerging technologies, development more effective intervention strategies warrant urgent investigation.

Language: Английский

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Aflatoxin Exposure-Caused Male Reproductive Toxicity: Molecular Mechanisms, Detoxification, and Future Directions

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1460 - 1460

Published: Nov. 17, 2024

Widespread endocrine disorders and infertility caused by environmental food pollutants have drawn considerable global attention. Aflatoxins (AFTs), a prominent class of mycotoxins, are recognized as one the key contributors to contamination. Aflatoxin B

Language: Английский

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Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1527 - 1527

Published: Dec. 13, 2024

The NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is a potential therapeutic target for central nervous system diseases. This review emphasizes the role of oxidative stress and neuroinflammation in neurodegenerative diseases, highlighting Nrf2 activators such as dimethyl fumarate (DMF). DMF, initially administered treating psoriasis, has demonstrated efficacy multiple sclerosis metabolized to monomethyl fumarate, which may exert significant effects. DMF activates Nrf2-ARE pathway, recent studies have indicated that its anti-inflammatory effects occur through Nrf2-independent mechanisms. Electrophilic activators, covalently bind cysteine residues proteins modulate their function. We discuss implications residue modifications by cause both benefits off-target Furthermore, we propose chemical proteomics-based drug discovery approach achieve desired selectively modifying cysteines proteins. These findings advocate broader understanding mechanisms electrophilic thereby improving strategies diseases while minimizing toxicity.

Language: Английский

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Chemical Inhibition of NRF2 Transcriptional Activity Influences Colon Function and Oestrogen Receptor Expression in Mice at Different Ages

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13647 - 13647

Published: Dec. 20, 2024

We aim to investigate whether chemical inhibition of NRF2 transcriptional activity (TA) influences distal colon contractions, particularly in an age-dependent manner females, and it impacts oestrogen receptor signalling female mice. This study was performed on 3 6-month-old mice treated with ML385 (30 mg/kg) or a vehicle for 7 days (i.p.). The functionality verified bead expulsion test; serum samples were collected oestradiol levels, stored various histological analyses. results show that the seven-day treatment significantly downregulated TA (p < 0.05) impacted its contractility. Additionally, young females exhibited increase goblet cell number increased ERα, but not ERβ, especially older It is worth noting basal level membrane GPR30 higher within epithelial layer, led downregulation In summary, decreases contractility numbers. expression receptors colons

Language: Английский

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