Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 14, 2023

Doxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, alone or in combination variety of cancers, while it has been found to cause serious cardiac side effects clinical application. More more researchers are trying explore the molecular mechanisms DOX-induced cardiomyopathy (DIC), which oxidative stress inflammation considered play significant role. This review summarizes signaling pathways related DIC compounds that exert cardioprotective by acting on relevant pathways, including role Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1α NOS, NOX, Fe2+ stress, as well NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB inflammation. Hence, we attempt explain terms inflammation, provide theoretical basis new idea for further drug research reducing DIC. Video Abstract.

Language: Английский

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Curcumin: Overview of Extraction Methods, Health Benefits, and Encapsulation and Delivery Using Microemulsions and Nanoemulsions

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8874 - 8874

Published: May 17, 2023

Curcumin is the principal curcuminoid found in rhizomes of turmeric. Due to its therapeutic action against cancer, depression, diabetes, some bacteria, and oxidative stress, it has been used widely medicine since ancient times. low solubility, human organism cannot completely absorb it. Advanced extraction technologies, followed by encapsulation microemulsion nanoemulsion systems, are currently being improve bioavailability. This review discusses different methods available for curcumin from plant material, identification resulting extracts, beneficial effects on health, techniques into small colloidal systems that have over past decade deliver this compound.

Language: Английский

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Nanoparticles Hitchhike on Monocytes for Glioblastoma Treatment after Low-Dose Radiotherapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(14), P. 13333 - 13347

Published: July 5, 2023

Glioblastomas (GBMs) are aggressive primary brain tumors with fatal outcome. Traditional chemo-radiotherapy has poor therapeutic effect and significant side effects, due to the drug radiotherapy (RT) resistance, natural blood-brain barrier, high-dose RT damage. Even more, tumor-associated monocytes (macrophages microglia, TAMs) constitute up 30%-50% of GBM cellular content, tumor microenvironment (TME) in is extremely immunosuppressive. Here, we synthesized nanoparticles (D@MLL) that hitchhike on circulating target intracranial GBMs assistance low-dose RT. The chemical construction D@MLL was DOX·HCl loaded MMP-2 peptide-liposome, which could by surface modified lipoteichoic acid. First, at site increases monocyte chemotaxis induces M1 type polarization TAMs. Subsequently, intravenous injected targets hitchhikes them central area. then released response, inducing immunogenic cell death, releasing calreticulin high-mobility group box 1. This further contributed TAMs M1-type polarization, dendritic maturation, T activation. study demonstrates advantages delivered endogenous sites after RT, it provides a high-precision treatment for GBMs.

Language: Английский

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Managing Doxorubicin Cardiotoxicity: Insights Into Molecular Mechanisms and Protective Strategies

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 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.

Language: Английский

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Synergy, Additive Effects, and Antagonism of Drugs with Plant Bioactive Compounds

Drugs and Drug Candidates, Journal Year: 2025, Volume and Issue: 4(1), P. 4 - 4

Published: Feb. 5, 2025

Background/Objectives: The interaction of bioactive compounds derived from plants with drugs has become a significant area investigation due to its potential improve, reduce, or have no effect on therapeutic outcomes. Due the dual these interactions, elucidating underlying mechanisms is essential for establishing strategy. This study emphasizes findings, mechanisms, and clinical implications drug–plant interactions. It calls more studies seek safe effective incorporation into practice. Methods: To identify relevant studies, we performed systematic literature search based various scientific databases 11 August 2024 30 December 2024. will be keywords such as synergy, antagonism, plant compounds, drug interactions supplemented secondary terms phytochemicals, herb-drug pharmacokinetics, pharmacodynamics. Results: Plant bioactives, including polyphenols, flavonoids, alkaloids, terpenoids, display valuable biological activities that can interact medications in three principal ways: additive effects, antagonism. Synergy occurs when combined effects chemicals pharmaceuticals outweigh sum their separate increasing effectiveness allowing dosage decrease reduce adverse effects. Additive occur impact equals total individual resulting better outcomes without risk. Antagonism ingredient reduces counteracts medicine, thereby jeopardizing treatment. In addition, specific may discernible effect. chemical makeup chemicals, medication patient characteristics genetics metabolism all intricacy Conclusions: Pharmacokinetics pharmacodynamics considerably modulated through components, which cause efficacy increase toxicity agents. More are needed clarify action, prove relevance, create guidelines co-administration. integrative approach mitigate those risks allow optimization by introducing pharmacogenomics personalized medicine approaches.

Language: Английский

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Curcumin mitigates heatstroke-induced myocardial injury by modulating the Akt/Bad/Caspase-3 pathway

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151653 - 151653

Published: March 1, 2025

Language: Английский

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Doxorubicin-mediated cardiac dysfunction: Revisiting molecular interactions, pharmacological compounds and (nano)theranostic platforms

Environmental Research, Journal Year: 2023, Volume and Issue: 234, P. 116504 - 116504

Published: June 24, 2023

Language: Английский

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Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7ADR breast cancer cells

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Feb. 15, 2023

Abstract The members of the genus Phyllanthus have long been used in treatment a broad spectrum diseases. They exhibited antiproliferative activity against various human cancer cell lines. Breast is most diagnosed and leading cause death among women. Doxorubicin (DOX) an anticancer agent to treat breast despite its significant cardiotoxicity along with resistance development. Therefore, this study was designed assess potential cytotoxicity P. niruri extracts (and fractions) alone combination DOX naïve (MCF-7) doxorubicin-resistant lines (MCF-7 ADR ). methylene chloride fraction (CH 2 Cl ) showed cytotoxic all tested fractions. Interestingly, CH -fraction more MCF-7 than at 100 µg/mL. At sub-cytotoxic concentrations, enhanced effect both under investigation (IC 50 values 0.054 µg/mL 0.14 vs. 0.2 for MCF-7) (1.2 0.23 9.9 ), respectively. Further, TLC fractionation that B2 subfraction equitoxic exerted powerful synergism 0.03 alone) within . Untargeted metabolite profiling crude methanolic extract (MeOH) exhibiting conducted using liquid chromatography diode array detector-quadrupole time-of-flight mass spectrometry (LC-DAD-QTOF). Further studies are needed separate active compounds from elucidate their mechanism(s) action.

Language: Английский

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Genistein and/or sulfasalazine ameliorate acetic acid-induced ulcerative colitis in rats via modulating INF-γ/JAK1/STAT1/IRF-1, TLR-4/NF-κB/IL-6, and JAK2/STAT3/COX-2 crosstalk

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 214, P. 115673 - 115673

Published: July 4, 2023

Language: Английский

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Exploring the mechanism of curcumin in the treatment of doxorubicin-induced cardiotoxicity based on network pharmacology and molecular docking technology

Medicine, Journal Year: 2024, Volume and Issue: 103(7), P. e36593 - e36593

Published: Feb. 16, 2024

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents. However, nonselective effect leads to serious cardiotoxicity risk in clinical use. Curcumin a well-known dietary polyphenol that showed protective against cardiotoxic DOX. This study aimed assess role curcumin protection DOX-induced cardiotoxicity. Potential compound and disease targets were obtained from relevant databases, common screened. Protein-protein interaction (PPI) was used predict core targets. Gene ontology (GO) bioprocess analysis Kyoto encyclopedia genes genome enrichment enriched possible biological processes (BP), cellular components, molecular function, signaling pathways involved. Finally, binding target proteins evaluated through docking. The docking score verified reliability prediction results. In total, 205 700 identified. A topological PPI network revealed 10 including TP53, tumor necrosis factor-alpha (TNF), AKT1, vascular endothelial growth factor (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), signal transducer activator transcription 3 (STAT3), HIF1A, MYC, epidermal receptor (EGFR), CASP3 (Caspase-3). Furthermore, analyses indicated effects mediated by related oxidation, inflammation, toxification, cell proliferation, migration, apoptosis, wounding, metabolism, proteolysis, pathway calcium (Ca2+). Molecular could bind with strong force, exhibiting good activity. has multi-cardioprotective modulating targets' expression elucidated key provided theoretical basis for further exploring prevention treatment

Language: Английский

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