Search Results (237)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis by promoting Aβ accumulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the antioxidant response, influencing genes involved in OS mitigation, mitochondrial function, and inflammation. Dysregulation of NRF2 is implicated in AD, making it a promising therapeutic target. Emerging evidence suggests that adherence to a Mediterranean diet (MD), which is particularly rich in polyphenols from extra virgin olive oil (EVOO), is associated with improved cognitive function and a reduced risk of mild cognitive impairment. Polyphenols can activate NRF2, enhancing endogenous antioxidant defenses. This study employs a computational approach to explore the potential of bioactive compounds in EVOO to modulate NRF2-related pathways in AD. We analyzed transcriptomic data from AD and EVOO-treated samples to identify NRF2-associated genes, and used chemical structure-based analysis to compare EVOO’s bioactive compounds with known NRF2 activators. Enrichment analysis was performed to identify common biological functions between NRF2-, EVOO-, and AD-related pathways. Our findings highlight important factors and biological functions that provide new insight into the molecular mechanisms through which EVOO consumption might influence cellular pathways associated with AD via modulation of the NRF2 pathway. The presented approach provides a different perspective in the discovery of compounds that may contribute to neuroprotective mechanisms in the context of AD. Full article

Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of cancer, including parotid gland cancers. This study aimed to assess whether blood prooxidant–antioxidant markers could aid in diagnosing and guiding surgery for recurrent malignancies after parotid tumor treatment. Methods: We examined patients (n = 20) diagnosed with WT (n = 14) and PA (n = 6) using histopathological verification and computed tomography (CT) who qualified for surgical treatment. Blood samples were taken before the surgery and again 10 days later for biochemical analysis. The activities of the antioxidant enzymes (SOD, CAT and GPx), the non-enzymatic antioxidants (GSH and UA) and oxidative stress markers (MDA and TOS) were determined in the blood. The activities of CK and LDH and the concentrations of Cor and TAS were measured in the serum. Hb and Ht were determined in whole blood. Results: The patients’ SOD, CAT, and GPx activities after surgery did not differ significantly from their preoperative levels. However, following surgery, their serum TOS levels were significantly elevated in all the patients compared to baseline. In contrast, the plasma MDA concentrations were markedly reduced after surgery. Similarly, the GSH concentrations showed a significant decrease postoperatively. No significant changes were observed in the CK and LDH activities, TAS concentrations, or levels of Hb, Ht and Cor following surgery. Conclusions: The surgical removal of salivary gland tumors did not result in a reduction in oxidative stress at 10 days after surgery. Therefore, further studies are needed to determine the effectiveness of endogenous defense mechanisms in counteracting the oxidative stress induced by salivary gland tumors. Full article

Alcohol dependency is a complex and chronic condition that negatively impacts multiple organ systems, including the skin. A key pathological factor in this process is oxidative stress, leading to progressive cellular damage, chronic inflammation, and accelerated cutaneous aging. Alcohol metabolism generates reactive oxygen species (ROS), which overwhelm endogenous antioxidant defenses and contribute to a range of skin alterations, including nonspecific changes such as xerosis, erythema, and wrinkle formation, as well as inflammatory and neoplastic skin disorders. Additionally, alcohol-induced alterations of the skin microbiome may further exacerbate skin barrier dysfunction and inflammatory responses. This review explores the biochemical mechanisms and skin microbiome alterations linking alcohol-induced oxidative stress to skin damage and disease. Furthermore, it evaluates the therapeutic potential of antioxidant-based interventions, both natural and synthetic. Antioxidants may offer protective and regenerative effects by scavenging free radicals, modulating inflammatory responses, and enhancing skin barrier function. The paper aims to provide a comprehensive overview of the molecular and microbial interplay between alcohol, oxidative stress, and skin health, while identifying future directions for targeted antioxidant therapy in individuals with alcohol dependency. Full article

Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model of chemically induced OA. Forty male Wistar rats (8–9 weeks old) received intra-articular sodium monoiodoacetate (Mia) to induce OA, and were subsequently treated with GSC. Inflammatory and oxidative stress parameters were analyzed at the end of the experiment. GSC supplementation enhanced endogenous antioxidant defenses, suggesting systemic antioxidant activity. However, no histological improvement was observed. In silico analyses indicated that Mia-induced OA may involve a complex molecular environment that GSC, at the tested dose, failed to modulate at the site of injury. Despite the limited local effects, these findings support the systemic benefits of GSC and highlight the potential of natural compound-based strategies in OA management. Given the adverse effects of conventional pharmacotherapy, the development of alternative, naturally derived treatments remains a promising avenue for future research. Full article

Diabetes is the world’s leading cause of renal and premature cardiovascular disease. There are marked differences between groups of patients with different ethnicities in their susceptibility to diabetes and its renal and cardiovascular complications. Novel markers of developing diabetes complications are related to disturbances in oxidative metabolism. In this cross-sectional study, we measured the arterial stiffness in patients of differing ethnicities with type 2 diabetes mellitus and assessed the relationship of their ethnicity with systemic markers of oxidative stress. Patients from black, African and Caribbean, and Asian minor ethnic groups were studied, with white patients with T2DM (n = 170) without evidence of cardiovascular disease (CVD). The vascular stiffness was measured by infrared finger-photoplethysmography. The oxidative stress burden was assessed by measuring the urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), activities of plasma glutathione peroxidase (GPx-3), superoxide dismutase (SOD) activities, and concentration of selenium. The vascular stiffness and 8-OHdG were higher in the white than in the Black patients (9.68 m/s vs. 9.26 m/s, p = 0.021 and 292.8 ng/mL vs. 200.9 ng/mL, p = 0.0027, respectively). Meanwhile, the GPx-3 and SOD activities and selenium were lower in the white than in the Black patients (283.3 U/L vs. 440.4 U/L, p < 0.0001; 37.5 U/L vs. 75.6 U/L, p = 0.0007; and 1.14 vs. 1.28 µmol/L, p = 0.0001, respectively). In regression modelling, the 8-OHdG/creatinine ratio was an independent predictor of vascular stiffness in the white patient group (β = 0.23 m/s per unit increase in ln(8-OHdG/creatinine) [95% CI, 0.03 to 0.42]; p = 0.021) but not in the Black patient group (p = 0.29). Increased vascular stiffness, lower endogenous antioxidant defense, and greater levels of oxidative damage were found in patients of white ethnicity, which could contribute to the higher incidence of CVD compared with patients from Black minor ethnic groups with diabetic renal disease. Full article

One of the critical challenges in assisted reproductive technology (ART) is the inadequacy of effective regulation of reactive oxygen species. Simultaneously, the endogenous antioxidant defense system plays a significant role in combating oxidative stress across various physiological stages of embryonic development. However, these intrinsic defense systems alone are insufficient as they rely on exogenous antioxidants that interact synergistically to enhance and sustain antioxidant capacity. Considering the principal role of antioxidants in mitigating oxidative stress in oocyte growth, identifying reliable and non-toxic antioxidants is an essential prerequisite for effective therapeutic applications. Thus, owing to the need to explore exogenous antioxidants, we attempted to summarize and analyze the literature data defining the potential use of curcumin in mitigating oxidative stress to promote oocyte maturation through in vivo and in vitro model studies. Recent studies demonstrated the protective role of curcumin against oxidative stress and the inflammatory response, primarily through the upregulation of key antioxidant enzymes (including SOD, CAT and GPx), a reduction in oxidative stress markers (e.g., ROS, MDA) and by suppressing the pro-inflammatory signaling pathways (such as NF-kB, JAK/STAT) while activating the NRF2/HO-1 pathway to further enhance the cellular antioxidant defense. Advancing curcumin as a therapeutic agent necessitates a thorough understanding of curcumin’s molecular mechanisms and targeted pharmacological effectiveness to treat female infertility, and despite the progress in enhancing curcumin’s bioavailability, the optimal dosing strategies still need to be defined. Future studies are required to develop strategies to augment antioxidant defense mechanisms (modeling in vivo and in vitro studies) using curcumin with a specific emphasis on curcumin’s role in improving mitochondrial activity. This approach is expected to represent a significant advancement in the field of medicine, offering novel therapeutic possibilities. Full article

Ellagic acid (EA) is a natural polyphenol found in various fruits, nuts, and mushrooms. It exhibits a variety of biological activities, including potent antioxidant, anti-inflammatory, anti-obesity, and neuroprotective properties. EA exerts hepatoprotective effects through multiple mechanisms, including (1) scavenging reactive oxygen species (ROS) and enhancing endogenous antioxidant defenses (e.g., by activating Nrf2/ARE), (2) modulating inflammatory signaling pathways (e.g., inhibiting NF-κB, TNF-α, and IL-6), and (3) regulating apoptosis (e.g., downregulating the Bax/Bcl-2 ratio) and fibrosis (e.g., inhibiting TGF-β/Smad signaling). Despite its promising preclinical efficacy, the clinical applicability of EA is currently limited by its poor bioavailability. This could potentially be overcome by advanced delivery systems or by directly administering its active microbial metabolites, known as urolithins. EA and its derivatives also modulate the gut microbiota, promoting the growth of beneficial species and reducing gut permeability and hepatic inflammation. Preliminary clinical trials and other emerging evidence suggest that EA may reduce liver inflammation, oxidative stress, and metabolic dysregulation. However, more extensive human studies are needed to confirm its efficacy and safety in managing liver disease. This review highlights the therapeutic potential of EA in the treatment of liver diseases, particularly metabolic-dysfunction-associated steatotic liver disease (MASLD). Full article

Heavy metals are naturally occurring elements that have numerous applications in industries, agriculture, and other sectors, leading to their widespread distribution in the environment. The constant emission of heavy metals into the environment raises concerns about their impact and harmful effects on living organisms, including human health. Key threats arise from exposure to heavy metals such as lead, cadmium, mercury, and arsenic, all of which are classified as carcinogens. Chronic exposure and bioaccumulation of these metals can result in toxic effects on various body systems, including the female reproductive system. Notably, heavy metals can induce oxidative stress, generate excessive reactive oxygen species, and impair antioxidant defense systems. These metals may also lead to DNA damage, enzyme inactivation, and epigenetic modifications, ultimately disrupting critical cellular processes such as growth, proliferation, differentiation, repair, and apoptosis. Furthermore, some heavy metals can mimic endogenous estrogens, interact with estrogen receptors, and cause hormonal disruptions, a mechanism particularly relevant to the pathogenesis of female-related cancers. Despite significant advances, many gaps remain in our understanding of the molecular mechanisms by which heavy metals contribute to cancer development. Addressing these gaps could facilitate the development of more effective strategies for the prevention and treatment of female cancers. This review highlights the potential effects of heavy metals on molecular pathways in female cancers, suggesting several mechanisms of cancer development. Full article

Mitochondria play a central role in energy metabolism and continuously adapt through dynamic processes such as fusion and fission. When the balance between these processes is disrupted, it can lead to mitochondrial dysfunction and increased oxidative stress, contributing to the development and progression of various cardiometabolic diseases (CMDs). Their role is crucial in diabetes mellitus (DM), since their dysfunction drives β-cell apoptosis, immune activation, and chronic inflammation through excessive ROS production, worsening endogenous insulin secretion. Moreover, sympathetic nervous system activation and altered dynamics, contribute to hypertension through oxidative stress, impaired mitophagy, endothelial dysfunction, and cardiomyocyte hypertrophy. Furthermore, the role of mitochondria is catalytic in endothelial dysfunction through excessive reactive oxygen species (ROS) production, disrupting the vascular tone, permeability, and apoptosis, while impairing antioxidant defense and promoting inflammatory processes. Mitochondrial oxidative stress, resulting from an imbalance between ROS/Reactive nitrogen species (RNS) imbalance, promotes atherosclerotic alterations and oxidative modification of oxidizing low-density lipoprotein (LDL). Mitochondrial DNA (mtDNA), situated in close proximity to the inner mitochondrial membrane where ROS are generated, is particularly susceptible to oxidative damage. ROS activate redox-sensitive inflammatory signaling pathways, notably the nuclear factor kappa B (NF-κB) pathway, leading to the transcriptional upregulation of proinflammatory cytokines, chemokines, and adhesion molecules. This proinflammatory milieu promotes endothelial activation and monocyte recruitment, thereby perpetuating local inflammation and enhancing atherogenesis. Additionally, mitochondrial disruptions in heart failure promote further ischemic injury and excessive oxidative stress release and impair ATP production and Ca²⁺ dysregulation, contributing to cell death, fibrosis, and decreased cardiac performance. This narrative review aims to investigate the intricate relationship between mitochondrial dysfunction and CMDs. Full article

Background/Objectives: Oral health is a complex concept involving physical, psychological, emotional, and social components. A key factor in maintaining oral tissue integrity is redox balance, which is disrupted by oxidative stress (OS) through an imbalance between reactive oxygen species (ROS) and antioxidant defenses. This study examines the contribution of endogenous and exogenous sources to OS and explores the therapeutic potential of medicinal plants from the Asteraceae and Lamiaceae families in restoring redox homeostasis and improving oral health. Methods: A literature review was conducted, analyzing the role of OS in oral diseases and the antioxidant mechanisms of selected Asteraceae species. Special attention was given to their phytochemical contents—polyphenols, flavonoids, and essential oils—and their biological relevance to oral health. Results: OS plays a critical role in the onset and progression of oral conditions such as caries, periodontitis, gingivitis, aphthous ulcers, abscesses, precancerous lesions, and oral cancers. ROS and reactive nitrogen species (RNS) cause inflammation, tissue breakdown, and salivary gland dysfunction. Asteraceae plants like Matricaria chamomilla, Calendula officinalis, Cichorium intybus, Taraxacum officinale, Arctium lappa, Achillea millefolium, and Solidago virgaurea demonstrate notable antioxidant, anti-inflammatory, and antimicrobial properties that help counteract OS and support oral homeostasis. Conclusions: Asteraceae and Lamiaceae species show high therapeutic potential in addressing OS-related oral disorders. Their bioactive compounds aid in restoring redox balance and protecting oral tissues. These findings support the integration of phytotherapeutic agents into oral healthcare and call for further clinical validation of plant-based strategies for disease prevention and management. Full article

Lysine carboxymethyl cysteinate (LCC) is a synthetic substance obtained via lysine salification of S-carboxymethyl-cysteine. LCC has emerged as a promising glutathione (GSH) precursor. In this study, we sought to determine whether LCC could boost GSH levels and protect skin against oxidative stress. Experiments utilizing primary human keratinocytes and skin tissue samples revealed that LCC significantly increased endogenous GSH levels. LCC was able to pass through the stratum corneum and reach deep into the epidermis, where it enhanced the production of key metabolites involved in GSH biosynthesis. Then, the efficacy of LCC on skin protection was explored. LCC demonstrated protective effects by shielding keratinocytes from blue-light-induced oxidative stress and preventing ultraviolet B (UVB)-induced barrier disruption and pigmentation in a pigmented living skin equivalent (pLSE) model. In addition to its antioxidant properties, LCC also reduced the production of inflammatory mediators. Together, these findings underscore the multifaceted role of LCC in bolstering the natural antioxidant defenses of skin and preventing the accumulation of irreversible damage from the environment, thereby positioning it as a promising candidate for advancing skin health. Full article

Heat stress triggers systemic oxidative stress that compromises physiological homeostasis. This study evaluated methionine’s effects on hepatic and renal antioxidant capacity in heat-stressed Rex rabbits. Rabbits were divided into five groups (30 replicates/group): control (20–25 °C, basal diet), heat stress (HS, 30–34 °C, basal diet), and HS +0.15%, 0.3%, or 0.45% methionine-supplemented groups. After 21 days, serum, skin, liver, and kidney samples were analyzed for biochemical parameters, oxidative stress markers, and gene expression. Results showed that 0.15–0.3% methionine supplementation under heat stress increased methionine apparent digestibility and suppressed amino acid catabolism; decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels; reduced skin malondialdehyde (MDA) and elevated (MSRA) activity; attenuated hepatic central venous congestion and renal tubular vacuolization; enhanced hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities (0.3% group); and modulated antioxidant gene expression via Nrf2/HO-1 and Nrf2/NQO1 pathways. Pathological analysis confirmed reduced fibrosis and cellular damage in liver/kidney tissues. Optimal methionine supplementation (0.3%) effectively mitigated heat-induced oxidative organ damage by enhancing endogenous antioxidant defenses and regulating redox-sensitive signaling pathways. These findings provide a nutritional strategy for alleviating heat stress-related metabolic disorders in rabbits. Full article

Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation. Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n = 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards. Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca²⁺ by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p < 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p < 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p < 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model. Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment. Full article

Background: Oxidative stress is a key therapeutic target in neurological disorders. As processing wastes from the peanut industry, peanut skins are great sources of antioxidants and possess potential in neuroprotection. Methods: We prepared a peanut skin extract (PSE) and investigated its protective effects against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HT-22 neuronal cells. Results: PSE was rich in phenolic compounds (123.90 ± 0.46 mg GAE/g), comprising flavonoids (75.97 ± 0.23 mg RE/g) and proanthocyanidins (53.34 ± 1.58 mg PE/g), and displayed potent radical scavenging activities in chemical-based assays. In HT-22 cells, PSE pretreatment restored oxidative balance and endogenous antioxidant defense disrupted by t-BHP, as evidenced by significant reductions in ROS generation and lipid peroxidation levels, along with enhanced endogenous antioxidants. Specifically, 25 μg/mL PSE pretreatment reduced ROS levels by 53.03%, decreased MDA content by 78.82%, enhanced superoxide dismutase (SOD) activity by 12.42%, and improved the ratio of glutathione (GSH) to oxidized glutathione (GSSG) by 80.34% compared to the t-BHP group. Furthermore, PSE rescued mitochondrial membrane potential collapse, inhibited cytochrome c (Cyt.c) release, and prevented subsequent apoptotic death. Notably, the neuroprotective efficacy of PSE was comparable to that of edaravone, an approved neuroprotective drug. Mechanistic investigations combining network pharmacology and experimental validation revealed that the PI3K/Akt/Nrf2 signaling pathway played a pivotal role in mediating the neuroprotective effects of PSE. Compared to t-BHP-treated cells, 25 µg/mL PSE pretreatment significantly upregulated PI3K/Akt phosphorylation, the expression of Nrf2, and its downstream antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1). Conclusions: Collectively, these findings demonstrate the potential of PSE as a natural protective agent against oxidative-related neurological disorders. Full article

Background: Ozone therapy is used for its immunomodulatory, antioxidant, and analgesic properties in several fields. It can be useful in the rehabilitation of musculoskeletal disorders. Studies showed that O₂-O₃ therapy can reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis. Only a few studies have been published about the efficacy of this treatment in upper limb disease. Objective: The aim of this study is to investigate the use of ozone therapy in upper limb pathologies, evaluating its quantity, quality, and reported results in upper limb musculoskeletal disease, supraspinatus tendinopathy, shoulder impingement, adhesive capsulitis, chronic epicondylitis, and carpal tunnel syndrome. O₂-O₃ reduces inflammation by stimulating anti-inflammatory cytokines and inactivating pro-inflammatory molecules, relieves pain by interacting with pain receptors and improving blood circulation, promotes the regeneration of damaged tissues by stimulating growth factors and improving vascularization, and, finally, activates endogenous antioxidant defense systems by protecting cells from oxidative damage. Methods: A comprehensive search was conducted on PubMed and Scopus using the following MeSH terms: ozone therapy, infiltration joint, musculoskeletal disease, rehabilitation, upper limb, shoulder, wrist, hand, elbow, including English papers published in the last five years. Results: Five papers have been selected: four randomized controlled trials and one retrospective cohort study. The RCTs compared the effectiveness of intra-articular ozone injection with steroid injection alone or with other conservative treatments in shoulder diseases; one paper studied the effectiveness of ozone injection and orthoses in carpal tunnel syndrome compared to orthoses alone; one paper used ozone injections compared with steroid injection in patients with chronic lateral epicondylitis. A total of 218 patients were studied in these trials. Conclusions: Ozone treatment seemed to improve pain and function as well as other therapies in upper limb musculoskeletal disease. However, the trials’ protocols and the upper limb areas treated are different. Further studies are needed to define the effectiveness of ozone therapy in upper limb diseases in rehabilitation fields. Full article