Oxid Med Cell Longev
· 2025 · PMID 40761766
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As we age, cerebral endothelial cells (CECs) are less efficient in maintaining genome integrity and accumulate DNA damage. DNA damage in the brain endothelium can lead to the impairment of the blood-brain barrier (BBB),...As we age, cerebral endothelial cells (CECs) are less efficient in maintaining genome integrity and accumulate DNA damage. DNA damage in the brain endothelium can lead to the impairment of the blood-brain barrier (BBB), which is a major factor in brain dysfunction and dementia. Thus, identifying factors that regulate DNA repair in the brain endothelium can prevent brain dysfunction associated with aging. E2F1 is a transcription factor that regulates the expression of genes associated with DNA repair, among other functions. We hypothesize that E2F1 is downregulated in the brain vasculature of mice with aging and that E2F1 upregulation can improve cognitive function. We found that in the brain endothelium, E2F1 was significantly less phosphorylated, which is associated with its transcriptional activity, in the brain vasculature of aged mice and cultured CEC derived from aged mice compared with those from young mice. We found that overexpression reduced DNA damage in cultured CEC, and targeting the brain vasculature to overexpress improved cognition and increased the expression of genes associated with BBB integrity in aged mice. From RNA sequencing data from cultured CEC, we found that overexpression significantly upregulated , which codes for aconitate decarboxylase-1 (ACOD1), an enzyme that produces itaconate. We also found that 4-octyl itaconate (4-OI), a derivative of itaconate, reduced DNA damage, promoted cell proliferation, and restored endothelial barrier function from oxidative stress in cultured CEC. Thus, our study identifies the E2F1-ACOD1 axis as a molecular pathway that can protect the brain endothelium from oxidative stress and aging.
B Ramegowda L, Vishwanath P, V Salimath P
… +4 more, S Shetty M, K Marulaiah S, C Ramachandra S, Prashant A
Oxid Med Cell Longev
· 2025 · PMID 40756379
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Diabetic nephropathy (DN), a major complication of diabetes mellitus (DM) and a leading cause of end-stage renal disease (ESRD) globally, is characterized by oxidative stress (OS), chronic inflammation, and progressive f...Diabetic nephropathy (DN), a major complication of diabetes mellitus (DM) and a leading cause of end-stage renal disease (ESRD) globally, is characterized by oxidative stress (OS), chronic inflammation, and progressive fibrosis. Despite existing treatment options, disease progression remains a challenge. This study evaluates the therapeutic potential of vitamin D, alone and in combination with metformin, in mitigating DN progression in streptozotocin (STZ) induced diabetic rats. Male Wister rats were induced with diabetes using a single intraperitoneal injection of STZ and randomized into seven groups. Treatment regimens included vitamin D (5000 or 8000 IU), metformin (250 mg), or a combination, administered over 12 or 21 weeks. Fasting blood glucose (FBG), lipid profiles, renal function markers, and OS indicators were assessed. Renal tissues were examined via histopathological analysis to assess structural changes, and immunohistochemistry (IHC) was performed to evaluate the expression of key proteins involved in inflammation (transforming growth factor-beta [TGF-β]), fibrosis (VEGF), and OS (nuclear factor erythroid 2-related factor 2 [Nrf2]), and vitamin D receptor (VDR) signaling. Vitamin D treatment caused a dose-dependent decrease in FBG, with the vitamin D and metformin combination therapy achieving the greatest decrease (-49.8%) by week 21. Triglyceride levels were significantly reduced (-50%), while HDL levels remained stable. Combination therapy significantly reduced hydrogen peroxide (HO) (-36.84%) and nitric oxide (NO) (-14.29%) and enhanced antioxidant enzyme activity: glutathione reductase (GR) (+250%), Superoxide dismutase (SOD) (+11.33%), and Glutathione peroxidase (GPx) (+62.83%). Histological analysis revealed preserved renal architecture and reduced fibrosis in treated groups, particularly in those receiving combination therapy. IHC showed increased VDR and Nrf2 expression, reduced VEGF and TGF-β levels, reflecting attenuation of inflammation, fibrosis, and oxidative damage. Vitamin D, particularly in combination with metformin, significantly attenuates DN progression by enhancing metabolic control, reducing OS, and preserving renal function. These findings support its potential as an effective adjunctive therapy in DN management and provide a foundation for future clinical investigations.
Vasquez Gomez M, Filippa V, Acosta M
… +7 more, Mohamed F, Campo Verde F, Ferrari C, Jahn GA, Giménez MS, Ramirez DC, Gomez Mejiba SE
Oxid Med Cell Longev
· 2025 · PMID 40693021
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Mammary gland epithelial dysfunction is one of the serious consequences of subchronic dietary vitamin A deficiency (VAD). However, the underlying mechanism of this process is incompletely known. Consequently, we utilized...Mammary gland epithelial dysfunction is one of the serious consequences of subchronic dietary vitamin A deficiency (VAD). However, the underlying mechanism of this process is incompletely known. Consequently, we utilized a virgin rat model of dietary VAD (3 and 6 months) and subsequently intervened with a vitamin A sufficient (VAS) diet (0.5 or 1 month) prior to treatment completion. This experimental model allowed us to investigate the underlying molecular mechanism of mammary gland tissue dysfunction caused by VAD. Dietary VAD for 3 and 6 months caused increased inflammatory cell infiltration in the mammary gland parenchyma and glandular cells, with increased inflammation and apoptosis and reduced cell proliferation. These changes can be reversed with a VAS diet. Imbalances between the NF-κB and retinoic acid (RA) signaling pathways underlie mammary gland dysfunction following subchronic VAD. Nulliparous rats fed a VAD diet experience mammary gland epithelial dysfunction because of inflammation, apoptosis, and impaired cell growth.
AlAbduljader H, AlSaeed H, Alrabeea A
… +5 more, Sulaiman A, Haider MJA, Al-Mulla F, Ahmad R, Al-Rashed F
Oxid Med Cell Longev
· 2025 · PMID 40530326
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Metabolic-endotoxemia, characterized by the translocation of lipopolysaccharide (LPS) from Gram-negative bacteria into the bloodstream, is a key contributor to chronic low-grade inflammation associated with obesity and t...Metabolic-endotoxemia, characterized by the translocation of lipopolysaccharide (LPS) from Gram-negative bacteria into the bloodstream, is a key contributor to chronic low-grade inflammation associated with obesity and type 2 diabetes. This condition exacerbates metabolic disruptions by activating Toll-like receptor 4 (TLR4) on macrophages, leading to the release of pro-inflammatory cytokines and subsequent insulin resistance. Eicosapentaenoic acid (EPA; C20:5 (n-3)), an omega-3 polyunsaturated fatty acid, has demonstrated anti-inflammatory and antioxidative properties, but its precise mechanisms of action in mitigating LPS-induced stress remain unclear. This study investigates the pathways through which C20:5 (n-3) alleviates LPS-induced oxidative stress and inflammation in macrophages. C20:5 (n-3) pretreatment significantly reduced LPS-induced inflammatory responses, decreasing IL-1β and IL-6 expression and IL-1β secretion, and lowering the percentage of HLA-DR macrophages. C20:5 (n-3) also attenuated ER stress, evidenced by reduced expression of ATF4, DDIT3, HSPA5/GRP78, BIP, and CHOP at both gene and protein levels. Oxidative stress was mitigated, as shown by decreased HIF1α expression, reduced ROS levels, and preservation of mitochondrial membrane potential. Importantly, C20:5 (n-3) increased the expression of PPARα and FABP5 while inhibiting NF-κB activation independently of the TLR4-IRF5 pathway. The protective effects of C20:5 (n-3) was abolished by PPARα inhibition with GW9662, indicating that C20:5 (n-3)'s action is PPARα-dependent. This study highlights the modulatory role of C20:5 (n-3) in alleviating LPS-induced oxidative stress and inflammation in macrophages through activation of the FABP5/PPARα/NF-κB axis, independently of TLR4-IRF5 signaling. These findings reveal a novel mechanism for C20:5 (n-3)'s anti-inflammatory effects and suggest that targeting the FABP5/PPARα pathway may offer therapeutic potential for treating metabolic disorders associated with chronic inflammation.
Pinheiro EF, da Costa NSS, Martins ML
… +10 more, Saito GA, Assad N, Cardoso PB, Batista EJO, de Moraes SAS, Passos ADCF, Leão LKR, Gouveia A, Oliveira KRHM, Herculano AM
Oxid Med Cell Longev
· 2025 · PMID 40487383
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Efavirenz (EFV) is a medication widely used for the treatment of HIV-positive patients. Several studies have demonstrated that the prolongate use of EFV can lead to the development of neurological diseases, such as panic...Efavirenz (EFV) is a medication widely used for the treatment of HIV-positive patients. Several studies have demonstrated that the prolongate use of EFV can lead to the development of neurological diseases, such as panic syndrome, depression, and anxiety disorders. In this current study, we evaluate whether the ascorbic acid (AA) treatment can prevent anxiety-like behavior and brain oxidative stress induced by EFV treatment in zebrafish. Our data demonstrated that the EFV treatment induces anxiogenic-like behavior and intense lipid peroxidation in the zebrafish brain. The AA treatment was able to prevent both anxiogenic-like behavior and brain oxidative stress elicited by the EFV treatment. Therefore, our data provide robust evidence that the EFV induced anxiety-like behavior in zebrafish via a redox-dependent pathway and that AA treatment can minimize these adverse effects. Taken together, our preclinical study strongly suggests that the use of an AA-enriched diet can minimize the effects of EFV on the central nervous system (CNS) and improve the quality of life for patients undergoing EFV treatment.
Oxid Med Cell Longev
· 2025 · PMID 40458194
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The aim of this review is to draw attention to key findings from various published studies concerning the effect of methylcobalamin/cyanocobalamin on the immune response of patients diagnosed with pernicious anemia (PA)....The aim of this review is to draw attention to key findings from various published studies concerning the effect of methylcobalamin/cyanocobalamin on the immune response of patients diagnosed with pernicious anemia (PA). This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure the accuracy and reliability of the included randomized controlled trials (RCTs) evaluating the impact of vitamin B12, in either natural or synthetic form, on immune function in patients with PA. The protocol was registered with PROSPERO (CRD42024518621). Methylcobalamin/Cyanocobalamin administration in PA patients significantly increased CD3, CD8+, and CD19 cell levels, restoring them toward normal. Natural Killer (NK) cell activity improved, while the CD4/CD8 ratio decreased. These findings indicate a potential enhancement of immune function in PA patients. Significant restoration of CD3, CD8+, and CD19 cell counts was observed in PA patients after vitamin B12 administration, whether in its natural (methylcobalamin) or synthetic (cyanocobalamin) form. Additionally, NK cell activity was improved, and the CD4/CD8 ratio decreased. These findings suggest that methylcobalamin/cyanocobalamin has the potential to significantly enhance immunity in patients with PA. Therefore, we recommend conducting well-designed, large-scale Phase II and Phase III clinical trials with standardized methodologies to validate these findings and provide more robust evidence on the immunomodulatory effect of vitamin B12 in PA patients.
Hosseini E, Beyranvand Z, Schoenwaelder SM
… +2 more, Farhid F, Ghasemzadeh M
Oxid Med Cell Longev
· 2025 · PMID 40321407
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Premature activation of integrin plays a central role in the induction and development of the platelet storage lesion (PSL) characterized by an exhausted platelet phenotype that affects adhesion and spreading on fibr...Premature activation of integrin plays a central role in the induction and development of the platelet storage lesion (PSL) characterized by an exhausted platelet phenotype that affects adhesion and spreading on fibrinogen. Given the role of reactive oxygen species (ROS) in regulating platelet activation per se, we investigated the effects of a ROS scavenger on reducing the functional decline of platelet integrin during storage. Platelet-rich plasma-platelet concentrates (PRP-PCs) were either treated with ROS-reducing agents (1 mM N-acetyl-L-cysteine [NAC] or 30 μM NADPH oxidase [NOX] inhibitor, VAS2870) or kept untreated during storage. CD41/CD61 (total integrin ) expression and PAC-1 binding (specific to active integrin conformation) were analyzed by flow cytometry over a 5 day storage period. Molecular changes in integrin subunit were evaluated by western blotting. Platelet adhesion/spreading to fibrinogen in the presence of ROS inhibitors was also investigated during storage using fluorescence microscopy. A decrease in the molecular weight of integrin subunit was observed during platelet storage, and was significantly reduced by NAC but not VAS2870, suggesting proteolytic cleavage of during storage. Further to this, ROS inhibitors decreased integrin activation and increased platelet adhesion to fibrinogen from day 3 of storage, while NAC but not VAS2870 improved platelet spreading. This is the first report of increasing cleavage of integrin during storage that was inversely correlated with integrin -mediated platelet function. In this regard, as a generic ROS scavenger, NAC was shown to reduce defects in platelet spreading through inhibition of cleavage. This is in contrast to VAS2870 which selectively inhibits cytosolic NOX alone, suggesting that the reduced platelet function observed during storage may be due to cumulative effects of mitochondrial ROS. Taken together, these studies suggest that adding NAC to platelets may significantly preserve optimal integrin and platelet function during storage. Moreover, as a reversible scavenger, its inhibitory effect can be readily compensated after transfusion.
Azadmanesh M, Noorbakhsh MF, Nazifi S
… +1 more, Faraji M
Oxid Med Cell Longev
· 2025 · PMID 40225415
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This study intends to investigate the green synthesis of silver (Ag) and gold (Au) nanoparticles (NPs) using extract and to evaluate the antioxidant and anti-inflammatory effects of the synthesized NPs and the extract....This study intends to investigate the green synthesis of silver (Ag) and gold (Au) nanoparticles (NPs) using extract and to evaluate the antioxidant and anti-inflammatory effects of the synthesized NPs and the extract. In this study, aqueous and hydroalcoholic extracts of were prepared, which were used for the biosynthesis of Ag and Au NPs. Dynamic light scattering (DLS), zeta potential analysis, transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, UV-Vis spectroscopy, and X-ray diffraction (XRD) methods were used to characterize the green NPs. The antioxidant effect of the NPs was estimated using in vitro methods, including reducing power (RP), ferric reducing/antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH). To evaluate the anti-inflammatory and antioxidant activity of extract and Ag and Au NPs, we used the carrageenan method. In our experiment, the extract and the synthesized NPs were administered orally to the mice 2 h before the carrageenan injection. The subsequent inhibition of inflammation and reduction of paw thickness were quantified. To evaluate their antioxidant effect, malondialdehyde (MDA), and total antioxidant capacity (TAC) levels were measured. Levels of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor- (TNF-), were also quantified. In this study, the results indicate that the synthesized Ag and Au NPs have antioxidant and anti-inflammatory effects. The most promising results were observed in the groups that received the Ag NPs.
Oxid Med Cell Longev
· 2025 · PMID 40225414
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Monosodium glutamate (MSG) is the most commonly used food additive and has well-known neurotoxic effects. The current study was carried out to assess the underlying mechanisms of the neurotoxicity of MSG on the hippocamp...Monosodium glutamate (MSG) is the most commonly used food additive and has well-known neurotoxic effects. The current study was carried out to assess the underlying mechanisms of the neurotoxicity of MSG on the hippocampus in male rats and examine the protective effect of plasmalogens (Pls) on nuclear factor-B (NF-B) and p38 MAPK signaling pathways in the hippocampus using behavioral, biochemical, and immunohistochemical methods. Twenty-four male Wistar albino rats were divided into four groups for control or treatment with MSG (2 g/kg body weight) and/or Pls (100 mg/kg body weight). All doses were received orally for 28 days. Results show that plasmalogens ameliorate the levels of glucose, insulin, lipids, oxidative stress markers, antioxidant enzymes, AKT, and neurochemical markers. It also reduces the level of the inflammatory markers TNF-, NF-B, and p38 mitogen-activated protein kinase (MAPK). Histological and immunohistochemical alterations in hippocampal tissues were found to be augmented postexposure to Pls, suggesting that Pls have a potent ameliorative effect. We conclude that Pls exert anti-inflammatory, antioxidant, and antiapoptotic effects and counteract MSG-induced neurotoxicity by altering the NF-B and p38 MAPK signaling pathways.
Oxid Med Cell Longev
· 2025 · PMID 40225412
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The present study reports the protective effect conferred by scavenging mitochondrial oxidative stress (mtOS) in 5-fluorouracil (5-FU)-induced renal injury. 5-FU renal toxicity model was created by administering 5-FU (1...The present study reports the protective effect conferred by scavenging mitochondrial oxidative stress (mtOS) in 5-fluorouracil (5-FU)-induced renal injury. 5-FU renal toxicity model was created by administering 5-FU (12 mg/kg b.w. intraperitoneally [i.p.], for 4 days) to male BALB/c mice. The protective effect of mitochondria-targeted antioxidant (MTA), Mito-TEMPO coadministered at a dosage of 0.1 mg/kg b.w. i.p., was established in terms of levels/expressions of renal injury markers, histopathological alterations, oxidative DNA damage, proinflammatory markers, mtOS, mitochondrial dysfunction, and modulation of apoptotic proteins and apoptotic cell death. A significant rise in the levels of serum urea, uric acid, and creatinine was noted after 5-FU administration to the animals. Immunohistochemical and ELISA findings demonstrated significant decrease in podocin and conversely a significant increase in neutrophil gelatinase-associated lipocalin (NGAL) expression after 5-FU challenge. The histopathological analysis further revealed Bowman's capsule dilation, glomerular condensation, and vacuolar degeneration. Mito-TEMPO treatment significantly lowered renal injury markers, reversed the expressions of podocin and NGAL to normal, and restored normal histoarchitecture of renal tissue. Mitochondrial reactive oxygen species (mtROS), mtLPO, activity of mitochondrial enzyme complexes, and mitochondrial antioxidant defense status were significantly improved in Mito-TEMPO protected group as compared to the 5-FU group. Further, significantly decreased expression of 8-OHdG, reduction in apoptotic cell death, and modulation of apoptotic proteins Bax, Bcl-2, and caspase-3 were noted in Mito-TEMPO protected group, indicating its protective effect against 5-FU-induced renal injury. The approach of targeting mtOS using MTA, Mito-TEMPO, may prove as safe adjuvant in alleviating renal toxicity during 5-FU chemotherapy.
Langhans B, Strassburg CP, Röcken C
… +1 more, Kalthoff S
Oxid Med Cell Longev
· 2025 · PMID 40182762
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Aging is characterized by the progressive decline of physiological functions and is associated with an increasing risk for developing multiple age-related diseases. UDP-glucuronosyltransferase (UGT)1A enzymes detoxify a...Aging is characterized by the progressive decline of physiological functions and is associated with an increasing risk for developing multiple age-related diseases. UDP-glucuronosyltransferase (UGT)1A enzymes detoxify a variety of endo- and xenobiotic reactive metabolites, thereby acting as indirect antioxidants. A common genetic haplotype was shown to affect redox balance in humanized transgenic (htg) mice. Since oxidative stress is a main activator of cellular senescence, we aimed to investigate the role of genetic variants in the process of aging. Htg-WT htg-SNP mice were harvested at the age of either 12 weeks (young) or 18 months (aged). The effect of aging was examined by analyzing expression and activity, expression of senescence markers, and senescence-associated secretory phenotype (SASP) factors, as well as blood counts, serum parameter, and histological staining. In comparison to aged htg-WT mice, hepatic mRNA and protein expression as well as UGT activity were significantly reduced in aged htg-SNP mice. Moreover, elderly htg-SNP mice exhibited increased levels of oxidative stress, senescence markers, SASP factors, and peripheral leukocyte counts compared to the respective htg-WT mice. Consistent with these findings, we observed higher amounts of collagen and amyloid fibrils as well as an elevated senescence-associated β-galactosidase (SA-β-gal) activity in histological sections of the liver obtained from aged htg-SNP mice. Our data suggest an accelerated aging process caused by a common haplotype. Moreover, elderly individuals carrying the haplotype might exhibit an altered metabolism of drugs, which could necessitate dose adjustments.
Mehrabi A, Nuori R, Gaeini A
… +6 more, Amirazodi M, Mehrtash M, Esfahlani MA, Bahrami M, Bejeshk MA, Rajizadeh MA
Oxid Med Cell Longev
· 2025 · PMID 39959582
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High-intensity interval training (HIIT) is a form of interval exercise that enhances capacity and benefits well-being. Resveratrol is a naturally occurring polyphenol prevalent in grapes and red wine, demonstrating signi...High-intensity interval training (HIIT) is a form of interval exercise that enhances capacity and benefits well-being. Resveratrol is a naturally occurring polyphenol prevalent in grapes and red wine, demonstrating significant health effects on the body. This study sought to evaluate the synergistic effects of swimming HIIT and resveratrol intake on the expression of SIRTs 4, SIRTs 5, and superoxide dismutases (SOD1 and SOD2) in the frontal lobe of elderly rats. Forty-five male Wistar rats, aged 22 months, were categorized into five groups: the control group (CTL), the swimming HIIT group (Ex: Exercise), the swimming HIIT with resveratrol group (R + Ex), the resveratrol group (R), and the solvent control group (vehicle). The R + Ex group engaged in high-intensity interval swimming and ingested resveratrol (10 mg/kg/day via gavage) for 6 weeks. During the initial and final sessions of each week, blood samples from the rats in the Ex and R + Ex groups were collected for lactate analysis. The proteins SIRTs 4 and 5, as well as SODs 1 and 2, were quantified using the western blot approach. Integrating HIIT with resveratrol markedly enhanced the expression of SIRT4, SIRT5, and antioxidant enzymes in the frontal lobe of elderly rats. Resveratrol and HIIT, particularly their synergistic effects, provide antioxidant and antiaging benefits on the frontal lobe of aged rats.
Beegam S, Al-Salam S, Zaaba NE
… +2 more, Elzaki O, Nemmar A
Oxid Med Cell Longev
· 2025 · PMID 39959581
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Hypertension is a risk factor for vascular injury and thrombotic complications, and smoking tobacco is a risk factor for the development and exacerbation of hypertension. The influence of waterpipe smoke (WPS) on coagula...Hypertension is a risk factor for vascular injury and thrombotic complications, and smoking tobacco is a risk factor for the development and exacerbation of hypertension. The influence of waterpipe smoke (WPS) on coagulation and vascular injury in hypertension is not fully understood. Here, we evaluated the effects of WPS in mice made hypertensive (HT) by infusing angiotensin II (Ang II) for 42 days. On day 14 of the infusion of Ang II or vehicle (normotensive; NT), mice were exposed either to air or WPS for four consecutive weeks. Each session was 30 min/day for 5 days/week. The concentrations of tissue factor, von Willebrand factor, fibrinogen, and plasminogen activator inhibitor-1 were elevated in the HT + WPS group versus either HT + air or NT + WPS groups. Similarly, in the HT + WPS group, thrombogenicity was increased both in vivo and in vitro, compared with either HT + air or NT + WPS groups. In aortic tissue, adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule-1, and vascular adhesion molecule-1 were increased in the HT + WPS group versus the controls. Likewise, various proinflammatory cytokines and markers of oxidative stress augmented in the HT + WPS group compared with either HT + air or NT + WPS. DNA damage, cleaved caspase-3, and cytochrome C were increased in the HT + WPS group versus the controls. The immunohistochemical expression of nuclear factor erythroid 2-related factor 2 was increased in the HT + WPS group versus either HT + air or NT + WPS. Taken together, our findings show that WPS exposure intensified thrombogenicity and vascular damage in experimentally induced hypertension. Our data suggest that vascular toxicity of WPS may be exaggerated in hypertensive patients.
Kopytek M, Kolasa-Trela R, Malinowski KP
… +3 more, Ząbczyk M, Natorska J, Undas A
Oxid Med Cell Longev
· 2024 · PMID 39735712
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Exercise stress test-induced hypofibrinolysis and changes in circulating levels of several interleukins have been observed in aortic stenosis (AS). However, it is unknown whether the pattern of exercise-induced changes i...Exercise stress test-induced hypofibrinolysis and changes in circulating levels of several interleukins have been observed in aortic stenosis (AS). However, it is unknown whether the pattern of exercise-induced changes in oxidative stress differs between AS patients and controls and if the differences are associated with changes in fibrinolysis and inflammation. We studied 32 asymptomatic patients with moderate-to-severe AS and 32 controls of similar age, sex, and body mass index. We assessed plasma protein carbonyl (PC) concentrations, a marker of oxidative stress, in relation to interleukin (IL)-10 and -6 levels and fibrinolysis capacity, expressed as plasma clot lysis time (CLT) at four time points: at baseline, at peak exercise, 1 and 24 h after a symptom-limited exercise test. AS patients had 12.8% and 27% higher PC concentrations 1 and 24 h after exercise than controls (both < 0.05), with no differences at baseline and peak exercise. In AS patients, PC concentration was 8.3% higher at peak exercise compared to baseline followed by further PC increase (+12.8% at 1 h and +20.5% at 24 h) compared to peak exercise (all < 0.05). In controls, PC concentrations increased during exercise, reaching the highest values 1 h after exercise (+21.9%). In the AS group, PC concentrations at baseline correlated with AS severity measured as peak transvalvular velocity ( : = 0.49, < 0.05), mean (PG: = 0.42, < 0.05), and maximal transvalvular pressure gradients (PG: = 0.41, < 0.05). PC concentrations correlated with IL-10 levels 1 h ( = 0.37, < 0.05) and 24 h ( = 0.38, < 0.05) post exercise in AS patients, whereas in controls only at baseline ( = 0.42, < 0.05). No associations between PC levels and IL-6 or CLT were observed at any time point. Our findings show that AS patients respond differently to exercise in terms of PC compared to controls, which suggests a novel effect of hemodynamic abnormalities in this disease on intensity of oxidative stress.
Matarrese P, Puglisi R, Mattia G
… +3 more, Samela T, Abeni D, Malorni W
Oxid Med Cell Longev
· 2024 · PMID 39735711
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Vitiligo is a skin disease that affects all ethnicities and genders and is characterized by the loss of pigment essentially due to the selective loss of melanocytes. Although it is generally considered a systemic disease...Vitiligo is a skin disease that affects all ethnicities and genders and is characterized by the loss of pigment essentially due to the selective loss of melanocytes. Although it is generally considered a systemic disease associated with polymorphisms in genes involved in the immune response, vitiligo is also considered an oxidative imbalance-associated disease. It represents a multifactorial pathology in which some genetic predisposition and epigenetic factors coupled with some critical biochemical and molecular pathways could play a pivotal role. The aim of this work was thus to review some of the fine cellular mechanisms involved in the etiopathogenesis of vitiligo, mainly focusing on the nonimmunological ones, extensively highlighted elsewhere. We took into consideration, in addition to oxidative stress, both the cause and the hallmark of the pathology, some less investigated aspects such as the role of epigenetic factors, e.g., microRNAs, of receptors of catecholamines, and the more recently recognized role of the mitochondria. Sex differences associated with vitiligo have also been investigated starting from sex hormones and the receptors through which they exert their influence. From literature analysis, a picture seems to emerge in which vitiligo can be considered not just a melanocyte-affecting disease but a systemic pathology that compromises the homeostasis of a complex tissue such as the skin, in which different cell types reside playing multifaceted physiological roles for the entire organism. The exact sequence of cellular and subcellular events associated with vitiligo is still a matter of debate. However, the knowledge of the individual biological factors implicated in vitiligo could help physicians to highlight useful innovative markers of progression and provide, in the long run, new targets for more tailored treatments based on individual manifestations of the disease.