Role of mesenchymal stem cells‐derived exosomes on inflammation, apoptosis, fibrosis and telocyte modulation in doxorubicin‐induced cardiotoxicity: A closer look at the structural level

Microscopy Research and Technique, Год журнала: 2024, Номер 87(7), С. 1598 - 1614

Опубликована: Март 5, 2024

Abstract Cardiotoxicity induced by doxorubicin (Dox) is a major complication in cancer patients. Exosomes (Ex) derived from mesenchymal cells could be promising therapeutic for various heart diseases. This study investigated the role of Ex Dox‐induced cardiotoxicity and its mechanistic insights, using Sacubitril/valsartan (S/V) as reference drug widely recommended failure management. The involved 24 Wistar rats, divided into control, Dox, Dox + S/V, groups. rats were assessed cardiac enzymes, inflammatory oxidative stress markers. Immunohistochemical expression caspase‐1, nuclear factor erythroid 2‐related 2 (NrF2), E‐Cadherin, CD117/c‐kit, Platelet‐derived growth factor‐α (PDGFα) was evaluated. P53 Annexin V PCR. Histological examination performed hematoxylin eosin Sirius red stains. ameliorated adverse pathological changes significantly decreased enzymes also exerted antifibrotic antiapoptotic effect tissue. treatment improved NrF2 immunohistochemistry, up‐regulated E‐Cadherin immune expression, restored telocyte markers CD117/c‐kit PDGFα. can mitigate acting an anti‐inflammatory, antioxidant, antiapoptotic, agents, restoring telocytes modulating epithelial transition. Research Highlights exhibit positive CD90 CD105 whereas showing −ve CD 34 flow cytometry. restore immunohistochemical alleviate myocardial apoptosis, fibrosis.

Язык: Английский

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Mechanistic insights into carvedilol's potential protection against doxorubicin-induced cardiotoxicity

European Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 200, С. 106849 - 106849

Опубликована: Июль 9, 2024

Doxorubicin (DOX) is an anthracycline chemotherapy drug widely employed in the treatment of various cancers, known for its potent antineoplastic properties but often associated with dose-dependent cardiotoxicity, limiting clinical use. This review explores complex molecular details that determine heart-protective effectiveness carvedilol relation to cardiotoxicity caused by DOX. The harmful effects DOX on heart cells could include oxidative stress, DNA damage, iron imbalance, disruption autophagy, calcium apoptosis, dysregulation topoisomerase 2-beta, arrhythmogenicity, and inflammatory responses. carefully reveals how serves as a strong protective mechanism, strategically reducing each aspect cardiac damage Carvedilol's antioxidant capabilities involve neutralizing free radicals adjusting crucial enzymes. It skillfully manages balance, controls restores balance essential cellular stability. Moreover, anti-apoptotic are outlined through adjustment Bcl-2 family proteins activation Akt signaling pathway. medication also 2-beta reduces renin-angiotensin-aldosterone system, together offering thorough defense against induced These findings not only provide detailed understanding into mechanisms coordinate protection offer considerable potential creation targeted strategies intended relieve chemotherapy.

Язык: Английский

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DOXORUBICIN AND CYCLOPHOSPHAMIDE MODE OF CHEMOTHERAPY–RELATED CARDIOMYOPATHY: REVIEW OF PRECLINICAL MODEL

Current Problems in Cardiology, Год журнала: 2024, Номер unknown, С. 102882 - 102882

Опубликована: Окт. 1, 2024

Язык: Английский

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Mesenchymal Stem Cell Derived Exosomes Ameliorates Doxorubicin-Induced Cardiotoxicity

Опубликована: Дек. 13, 2023

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there a need to discover innovative therapeutic approaches counteract DOX-induced (DIC). MSC-Exos have shown reduce apoptosis cardiac fibrosis promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of on ameliorating pyroptosis has not been investigated. In this current study H9c2 were first exposed DOX stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, further analysis performed through immunocytochemistry, western blotting, RT-PCR. Our data depicted post-treatment significantly (p<0.05) reduced HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, IL-18), executioner (GSDMD) DOX-treated cells. conclusion, our shows attenuates inflammation-induced vitro DIC model. findings indicate may serve promising intervention for mitigating DIC, they maintain capabilities MSCs while circumventing drawbacks associated traditional stem cell therapy.

Язык: Английский

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Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice

Biochemical Pharmacology, Год журнала: 2023, Номер 220, С. 116009 - 116009

Опубликована: Дек. 26, 2023

Язык: Английский

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Intratumoral Administration Immunogenic Exosomes can Modify Tumor Immune Microenvironment

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 2, 2024

It has been observed that external stress or stimuli can initiate apoptosis and produce extracellular vesicles known as exosomes. Recent studies suggest exosomes trigger an anti-tumor immune response. In the current study, secreted by 4T1 triple-negative breast cancer (TNBC) cell line under conditions (Dox, X-ray irradiation, cold plasma treatments) were studied. The stress-induced harvested, differing in their ability to present some DAMP proteins such HSP70 HMGB1. These enhance expression of pro-inflammatory molecules cells at different levels treatments. Additionally, intratumoral administration these shown modify tumor microenvironment (TIME) a TNBC murine model differently. We have concluded Dox treatment significantly reduce volume microenvironment. However, other methods immunogenic are neither effective nor appropriate. Nevertheless, many report significant therapeutic effects when used directly.

Язык: Английский

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Analysis and Validation of Critical Signatures and Immune Cell Infiltration Characteristics in Doxorubicin-Induced Cardiotoxicity by Integrating Bioinformatics and Machine Learning

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 669 - 685

Опубликована: Фев. 1, 2024

Purpose: Doxorubicin-induced cardiotoxicity (DIC) is a severe side reaction in cancer chemotherapy that greatly impacts the wellbeing of patients.Currently, there still an insufficiency effective and reliable biomarkers field clinical practice for early detection DIC.This study aimed to determine validate potential diagnostic predictive values critical signatures DIC.Methods: We obtained high-throughput sequencing data from GEO database performed analysis visualization using R software, GO, KEGG Cytoscape.Machine learning methods weighted gene coexpression network (WGCNA) were used identify key genes model construction.Receiver operating characteristic (ROC) nomogram assess their values.A multiregulatory was built reveal possible regulatory relationships signatures.Cell-type identification by estimating relative subsets RNA transcript (CIBERSORT) investigate differential immune cell infiltration.Additionally, animal constructed relationship between identified DIC.Results: Among 3713 differentially expressed genes, three (CSGALNACT1, ZNF296 FANCB) identified.A ROC curves based on showed excellent performance.The TFs CREB1, EP300, FLI1, FOXA1, MAX, MAZ modulated genes.An infiltration indicated many cells (activated NK cells, M0 macrophages, activated dendritic neutrophils) might be related progression DIC.Furthermore, may various degrees correlation cells.RT-qPCR demonstrated mRNA expression CSGALNACT1 significantly upregulated, while FANCB downregulated DOX-treated cardiomyocytes vitro vivo. Conclusion:Our suggested CSGALNACT1, associated with also involved DIC.They occurrence DIC.

Язык: Английский

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Unleashing the cardioprotective potential of Ezetimibe against Doxorubicin-induced cardiotoxicity in Wistar rats: Targeting oxidative stress and NF-κB-mediated inflammation

F1000Research, Год журнала: 2024, Номер 13, С. 1210 - 1210

Опубликована: Окт. 11, 2024

Background Doxorubicin (DOX) is a potent antineoplastic agent used in treating various adult and pediatric cancers, but it tends to provoke dose-dependent cardiotoxicity. Ezetimibe (EZE), cholesterol-lowering drug, has been reported possess defensive actions against oxidative stress inflammation, which are two of the main proposed mechanisms underlying development DOX-induced cardiotoxicity (DIC), hence, we aimed inspect possible protective effect EZE DIC rats. Methods 24 male Wistar rats were allocated into four groups six: control, DOX, 10 mg/kg plus DOX 20 DOX. At end study, experimental anesthetized blood samples collected for biochemical analysis, after hearts excised heart tissue obtained gene expression analyses. Results Pretreatment with at dose or alleviated cardiac damage induced by as blunted rise serum levels injury biomarkers, including troponin I (cTnI) N-terminal pro-B-type natriuretic peptide (NT-proBNP). Additionally, pretreating either mitigated elevating antioxidant enzymes superoxide dismutase (SOD) glutathione peroxidase (GPx), consequent reduction lipid peroxidation biomarker malondialdehyde (MDA) tissues. Furthermore, pretreatment hindered DOX-mediated where suppressed nuclear factor-kappa B (NF-κB) signaling negatively regulated its downstream proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) interleukin-1 beta (IL-1β) higher one. Conclusions Our findings indicate that exhibited cardioprotection rats, makes an interesting area further investigations, animal- human-wise, can pave way potential clinical application preventing future.

Язык: Английский

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Caffeic Acid Phenethyl Ester Suppresses Cytokine- and Chemotherapy-Induced Inflammation in Triple-Negative Breast Cancer via NF-κB Signalling

Natural Product Communications, Год журнала: 2024, Номер 19(11)

Опубликована: Ноя. 1, 2024

Background: Triple-negative breast cancer (TNBC) remains a significant clinical challenge due to its aggressive nature and lack of targeted therapies. In TNBC, inflammation contributes tumour progression by promoting cell proliferation, survival, migration. It may be triggered cytokines such as TNF-α or chemotherapeutic agents doxorubicin (DOX). Thus, identifying that suppress in TNBC is prime interest. Caffeic acid phenethyl ester (CAPE) naturally occurring anti-inflammatory compound exhibits selective cytotoxicity against some cells. However, impact on cytokine chemotherapy induced has not yet been explored. Aim: This study aimed investigate the effects CAPE TNF-α- DOX-induced metastatic markers TNBC. Methods: The DOX viability migration were assessed using MTT wound healing assays, respectively. effect expression pro-inflammatory cytokines, epithelial-mesenchymal transition (EMT) markers, invasion was evaluated RT-qPCR. Results: inhibited TNF-α-induced proliferation also suppressed upregulation NF-κB-regulated genes, IL-1B, IL-6, IL-8, TNF-α, corroborating evidence suppresses NF-κB signalling. Additionally, EMT TNF-α–stimulated DOX-treated cells downregulating vimentin VCAM1. Furthermore, reduced MMP2 MMP9. Conclusions: We demonstrated anticancer potential ability chemotherapy-induced inflammation. offers novel insights into role suppressing metastasis specifically context These findings underscore urgent need further possible adjuvant for treating patients with especially those undergoing chemotherapy.

Язык: Английский

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Prx5 overexpression protect against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via the TLR4/NF-κB pathway

International Immunopharmacology, Год журнала: 2024, Номер 146, С. 113788 - 113788

Опубликована: Дек. 19, 2024

Язык: Английский

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