Inhibition of NETs prevents doxorubicin-induced cardiotoxicity by attenuating IL-18-IFN-γ-Cx43 axis induced cardiac conduction abnormalities

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114016 - 114016

Опубликована: Янв. 12, 2025

Язык: Английский

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Managing Doxorubicin Cardiotoxicity: Insights Into Molecular Mechanisms and Protective Strategies

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(2)

Опубликована: Янв. 30, 2025

ABSTRACT Cancer ranks as the second leading cause of death in United States and poses a significant health challenge globally. Numerous therapeutic options exist for treating cancer, with chemotherapy being one most prominent. Chemotherapy involves use antineoplastic drugs, either alone or combination other medications, to target kill cancer cells. However, these drugs can also adversely affect healthy cells, various side effects. Among commonly used agents are anthracyclines, which include doxorubicin, daunorubicin, epirubicin. Doxorubicin is particularly notable its effectiveness but associated cardiotoxicity, common concern patients undergoing chemotherapy. Unfortunately, there currently no definitive treatment prevent reverse this cardiotoxicity. The cardiac effects doxorubicin manifest several ways, including changes electrocardiograms, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, heart failure, congestive failure. These complications may arise during treatment, shortly after it concludes, even weeks later. Various mechanisms have been proposed explain doxorubicin‐induced Key factors inhibition topoisomerase IIβ, mitochondrial damage, reactive oxygen species (ROS) production due iron metabolism, increased oxidative stress, heightened inflammatory responses, elevated rates apoptosis necrosis within tissue. This review article will provide comprehensive overview current state knowledge regarding cardiomyopathy. We explore underlying molecular contributing condition discuss emerging strategies aimed at mitigating impact on survivors.

Язык: Английский

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Sauchinone Preserves Cardiac Function in Doxorubicin-Induced Cardiomyopathy by Inhibiting the NLRP3 Inflammasome

Phytomedicine, Год журнала: 2025, Номер 140, С. 156624 - 156624

Опубликована: Март 6, 2025

Doxorubicin (Dox)-induced cardiomyopathy (DIC) is characterized by severe myocardial damage that can progress to dilated and potentially lead heart failure. No effective prevention or treatment strategies are available for DIC. Sauchinone, a diastereomeric lignan isolated from Saururus chinensis, known its notable anti-inflammatory effects. However, paucity of research on sauchinone in relation disease exists, particularly regarding role DIC, which remains unclear. This study aimed assess the therapeutic potential alleviating cardiac injury elucidate molecular mechanism Male C57BL/6J mice were used construct chronic acute DIC models vivo. The administered intragastrically concurrently with first injection Dox evaluate effect H9c2, rat cardiomyocyte cell line, was treated various concentrations conjunction protective effects vitro. Supplementation exogenous mitigated Dox-induced atrophy, fibrosis, ventricular remodeling, while preserving function. Sauchinone reduced abnormal apoptosis both vitro Additionally, restored mitochondrial function decreased reactive oxygen species levels, may be attributed activation nuclear factor erythroid 2-related 2 (NRF2) signaling, thereby attenuating oxidative damage. Furthermore, significantly inhibited NOD-like receptor thermal protein domain associated 3 (NLRP3) inflammasome infiltration inflammatory factors, stress inhibiting progression NLRP3 agonist nigericin abolished progression, antagonist MCC950 further enhanced beneficial vivo key novel finding present use sauchinone, effectively limits Specifically, not only alleviates but also delays Mechanistically, inactivation NRF2-mediated antioxidant pathways have been identified as two critical signaling regulated plays vital blocking holds promise approach cardiomyopathy.

Язык: Английский

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ROS-mediated ferroptosis and pyroptosis in cardiomyocytes: An update

Life Sciences, Год журнала: 2025, Номер unknown, С. 123565 - 123565

Опубликована: Март 1, 2025

Язык: Английский

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Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity

Cardiovascular Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Язык: Английский

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Buthionine sulfoximine acts synergistically with doxorubicin as a sensitizer molecule on different tumor cell lines

Journal of Toxicology and Environmental Health, Год журнала: 2025, Номер unknown, С. 1 - 23

Опубликована: Янв. 15, 2025

The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, clinical use is limited due side effects, including cardiotoxicity, myelosuppression, and resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse potentially reducing the required dose while maintaining efficacy. aim of present study was examine effects different concentrations BSO DOX, both individually combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 sarcoma), SVEC4–10 endothelial) cell lines. Cell viability, migration, clonogenicity were assessed using following assays MTT, scratch, colony formation. Antioxidant levels GSH, as well activities catalase (CAT), superoxide dismutase (SOD) measured. alone exhibited minimal cytotoxic reduced viability significantly. combination BSO+DOX decreased IC50 values most lines, demonstrating synergistic effect, especially B16/F10, S180, cells. significantly inhibited migration compared alone. While GSH treatment CAT SOD increased administration but remained unchanged by BSO. These suggest that may be considered valuable tool improve therapeutic efficacy, particularly cases chemotherapy-resistant tumors, enhances activity systemic toxicity.

Язык: Английский

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THE ROLE OF MATRIX METALLOPROTEINASE-9 AS A BIOLOGICAL MARKER IN HEART FAILURE

Russian Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Heart failure (HF) is an important medical, social and economic problem. The study of new biological markers deepens our understanding the pathogenesis this disease. In modern cardiology, there a growing interest in matrix metalloproteinases (MMPs). These enzymes play role tissue remodeling, angiogenesis, as well cell proliferation, migration differentiation. purpose literature review to analyze current experimental clinical data on MMP-9 diagnostic prognostic marker HF. This presents analysis publications given topic. We conducted sources covering all materials 01.11.2024. Experimental studies have established that key participant cardiac since it directly involved degradation extracellular proteins activation profibrotic pathways, cytokines chemokines. Clinical trial indicate significant importance for diagnosis prognosis patients with

Язык: Английский

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Inhibition of GRK2 reduced doxorubicin-induced oxidative stress and apoptosis through upregulating ADH1

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер unknown, С. 117261 - 117261

Опубликована: Фев. 1, 2025

Язык: Английский

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Inhibition of HSC proliferation and hepatic fibrogenesis with Erythrocyte membrane coated Doxorubicin/Black phosphorus nanosheets

International Journal of Pharmaceutics, Год журнала: 2025, Номер 673, С. 125403 - 125403

Опубликована: Фев. 25, 2025

Язык: Английский

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Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 26, 2025

Abstract The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in treatment recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone tumor immunotherapy, have emerged as one most promising advancements treatment. Although ICIs, such CTLA-4 PD-1/PD-L1 inhibitors, demonstrated clinical efficacy, their therapeutic impact remains suboptimal due patient-specific variability immune resistance. Cell death is fundamental process for maintaining tissue homeostasis function. Recent research highlights that combination induced regulatory cell (RCD) ICIs can substantially enhance anti-tumor responses across multiple types. In cells exhibiting high levels recombinant solute carrier family 7 member 11 (SLC7A11) protein, glucose deprivation triggers programmed (PCD) pathway characterized disulfide bond formation REDOX (reduction-oxidation) reactions, termed “disulfidptosis.” Studies suggest disulfidptosis plays critical role efficacy SLC7A11 cancers. Therefore, investigate potential synergy between this study will explore mechanisms both processes progression, with goal enhancing response targeting intracellular pathway.

Язык: Английский

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