Microvascular endothelial dysfunction in vascular senescence and disease

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 18, 2025

Cardiovascular disease (CVD) is the main cause of morbidity and mortality in adult elderly, with increasing prevalence worldwide. A growing body research has focused on earliest stage vascular decline-endothelial dysfunction (ED)-which at microvascular level can anticipate decades diagnosis CVD. This review aims to provide a prospect literature regarding development ED as an indissociable feature aging cardiovascular system, highlighting role inflammation process. Vascular consists lifelong continuum, which starts cell respiration its inherent production reactive oxygen species. Molecular imbalance followed by cellular epigenetic changes, modulate immune cells, such macrophage lymphocyte subtypes. These mechanisms are influenced lifestyle habits, affect hotspots organism, visceral fat gut microbiota. The process ultimately lead environment committed loss physiological functions endothelial cells. In addition, we discuss changes targeting connection between age-related dysfunction. Addressing represents critical endeavor order prevent or delay associated diseases.

Language: Английский

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Shikimic acid protects against doxorubicin-induced cardiotoxicity in rats

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 8, 2025

Abstract Doxorubicin (DOX) is used to treat a variety of malignancies; however, its cardiotoxicity limits effectiveness. Shikimic acid (SA) showed several promising biomedical applications. This study investigated the protective effect SA on DOX-induced in male rats. The ADMETlab 2.0 web server was predict pharmacokinetic properties SA. Molecular docking studies were conducted using AutoDock Vina. Fifty rats divided into 4 groups ( n = 10); G1 negative control; G2 injected with mg/kg DOX intraperitoneally (i.p.) once week for month; G3 gavaged by 1/10 LD 50 (280 mg/kg) daily month, and G4 as G3. After hematological, biochemical, molecular, histopathological investigations assessed. results that treatment led significant amelioration restoring inflammatory biomarkers, antioxidant gene expression, cardiac alterations. Importantly, impact against DOX-promoted deterioration targeting Nrf-2/Keap-1/HO-1/NQO-1 signaling pathway, which turn induces agents. These findings suggest could potentially mitigate toxicity during DOX-based chemotherapy.

Language: Английский

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Importance of systemic redox homeostasis biomarkers and transcription factors in patients undergoing open-heart surgery with cardiopulmonary bypass

Surgery Today, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Purpose Patients undergoing coronary artery bypass graft surgery and isolated valve disease may experience redox dyshomeostasis associated with cardiopulmonary (CPB). Methods We investigated the impact of CPB on systemic homeostasis by analyzing biomarkers antioxidant transcription factors preoperatively postoperatively using spectrophotometric immunochemical methods. Results Our findings indicate significant variations in protein oxidation biomarkers, capacity coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) levels after CPB. The ROC analysis indicated that carbonyl was valuable preoperative ( p = 0.009) postoperative 0.013) periods. also found glutathione peroxidase a biomarker during period 0.000). An catalase activity 0.017) before importance eliminating increased hydroperoxide load. graphs reinforced value PGC-1α 0.000) as biomarker, showing similar trend to Conclusion earlier view “increased oxidative stress decreased biofunction” has shifted exploring physiological role signaling regulation. believe future studies effects regulation processes through mechanisms will significantly contribute relevant literature.

Language: Английский

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Iron chelating, antioxidant and anti-apoptotic activities of hesperidin and/or rutin against induced-ferroptosis in heart tissue of rats

International Journal of Immunopathology and Pharmacology, Journal Year: 2025, Volume and Issue: 39

Published: March 1, 2025

Excess iron has been associated with cardiovascular diseases. Flavonoids are antioxidants and cardioprotectants. Therefore, the goal of current study is to evaluate anti-apoptotic, antioxidant, iron-chelating qualities two flavonoids, rutin (R) hesperidin (H), as well their potential prevent induced ferroptosis in rats. It an vivo cross-sectional study, which rats were divided into 12 groups; control, H, R, H + Fe, Fe IR, IR Ref, R R. Cardiac serum levels, troponin I, creatine kinase-MB (CK-MB), total binding capacity (TIBC), transferrin, ferritin, hepicidin determined. Moreover, levels malondialdehyde (MDA), nitric oxide (NO) glutathione (GSH) activities superoxide dismutase (SOD) peroxidase (GPx), also The expression DMT1, ACSL4, GPX4, Nrf2, caspase-3 genes evaluated by RT-qPCR. Lastly, a histological analysis heart tissues from several groups was conducted. After and/or treatment, our results revealed that cardiac markers (serum I CK-MB), metabolism iron, TIBC, DMT1 levels) oxidative stress (MDA, NO ACSL4 significantly ( P ⩽ 0.05) reduced, while antioxidant (GSH level, GPx SOD GPX4 Nrf2 increased. Also, exerted its protective anti-apoptotic role decreasing levels. Hesperidin treatment can be proposed therapeutic candidate attenuate ferroptosis.

Language: Английский

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Effects of Celastrol-Enriched Peanuts on Metabolic Health and the Development of Atherosclerosis

Nutrients, Journal Year: 2025, Volume and Issue: 17(9), P. 1418 - 1418

Published: April 23, 2025

Background: Celastrol, a pentacyclic triterpenoid active component isolated from the root bark of traditional medicinal plant Tripterygium wilfordii, displays significant anti-inflammatory, antioxidant, and immunomodulatory properties. However, its clinical application remains limited due to inadequate bioavailability. Methods: Regarding these issues, we innovatively developed novel peanut cultivar (cel-peanut) enriched with celastrol through distant hybridization combined metabolomics screening. Guided by research concept “natural anti-inflammatory diets for metabolic disease management”, established high-fat diet-induced ApoE−/− atherosclerotic mouse model systematically evaluate anti-atherosclerosis effects mechanisms cel-peanut. Results: Our results revealed that cel-peanut significantly reduced serum levels triglycerides (TGs) increased high-density lipoprotein cholesterol (HDL-C). Concurrently, markedly decreased lesion area enhanced collagen content within plaques. Mechanistic investigations demonstrated malondialdehyde (MDA) suppressed concentration pro-inflammatory cytokine IL-6 in lesions. Furthermore, promoted intestinal health modulating composition functionality gut microbiota, thereby attenuating atherosclerosis progression. Conclusions: Overall, findings indicate exerts therapeutic against microbiota-modulating This study proposes nutritional intervention strategy provides promising adjuvant treatment.

Language: Английский

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Activation of the Nrf2 Pathway by a Novel Bipyrazole Compound Mitigates Doxorubicin-Induced Cardiotoxicity in Wistar Albino Rats

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177731 - 177731

Published: May 1, 2025

Language: Английский

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Efficacy of Thymoquinone and Hesperidin in Attenuating Cardiotoxicity from 5-Fluorouracil: Insights from In Vivo and In Silico Studies

Toxics, Journal Year: 2024, Volume and Issue: 12(9), P. 688 - 688

Published: Sept. 23, 2024

5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that prevent these adverse effects without undermining anticancer efficacy crucial. This study investigates the Thymoquinone (TQ) and Hesperidin (HESP) preventing cardiotoxicity induced by 5-FU Wistar rats elucidates molecular interactions through docking studies. We employed an experimental design involving multiple groups exposed to 5-FU, with concurrent administration TQ HESP. Cardiac function markers, oxidative stress indicators, inflammatory markers were assessed. Additionally, was analyze interaction HESP key proteins. Treatment not only lowered levels cardiac enzymes also improved antioxidant capacity reduced inflammation tissues. Notably, combination provided more significant protective than either agent alone. Molecular supported findings, showing effective binding targets. demonstrate potential as agents against 5-FU-treated rats, their combined use offering enhanced protection. These findings suggest a viable strategy for reducing associated chemotherapy.

Language: Английский

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Quercetin protects the liver of broiler chicken against oxidative stress and apoptosis induced by ochratoxin A

Toxicon, Journal Year: 2024, Volume and Issue: 251, P. 108160 - 108160

Published: Nov. 1, 2024

Language: Английский

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Novelties in the pharmacological approaches for chronic heart failure: new drugs and cardiovascular targets

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: June 2, 2023

Despite recent advances in chronic heart failure (HF) management, the prognosis of HF patients is poor. This highlights need for researching new drugs targeting, beyond neurohumoral and hemodynamic modulation approach, such as cardiomyocyte metabolism, myocardial interstitium, intracellular regulation NO-sGC pathway. In this review we report main novelties on possible pharmacological targets therapy, mainly acting cardiac GCs-cGMP pathway, mitochondrial function calcium dysregulation.

Language: Английский

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Diabetic neuropathy: A NRF2 disease?

Journal of Diabetes, Journal Year: 2023, Volume and Issue: 16(9)

Published: Dec. 29, 2023

The transcription factor nuclear erythroid 2-related 2 (NRF2) has multifarious action with its target genes having redox-regulating functions and being involved in inflammation control, proteostasis, autophagy, metabolic pathways. Therefore, the controlled by NRF2 are pathogenesis of myriad diseases, such as cardiovascular syndrome, neurodegenerative autoimmune disorders, cancer. Amidst this large array diabetic neuropathy (DN) occurs half patients diagnosed diabetes appears an injury inflicted upon peripheral autonomic nervous systems. As a complex effector factor, entered spotlight during search new biomarkers and/or therapy targets DN. Due to growing attention for modulating several including DN, paper aims update recently discovered regulatory pathways oxidative stress, immunity. It presents animal models that further facilitated human studies regard modulation possibilities using DN biomarker therapy.

Language: Английский

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