Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy DOI Creative Commons

Sampat Singh Tanwar,

Sumeet Dwivedi,

Sheema Khan

и другие.

The Egyptian Heart Journal, Год журнала: 2025, Номер 77(1)

Опубликована: Март 10, 2025

Abstract Background Cardiomyopathy is a heterogeneous group of myocardial disorders characterized by structural and functional abnormalities the heart muscle. It classified into primary (genetic, mixed, or acquired) secondary categories, resulting in various phenotypes including dilated, hypertrophic, restrictive patterns. Hypertrophic cardiomyopathy, most common form, can cause exertional dyspnea, presyncope, sudden cardiac death. Dilated cardiomyopathy typically presents with failure symptoms, while rarer often associated systemic diseases. Diagnosis involves comprehensive evaluation history, physical examination, electrocardiography, echocardiography. Treatment options range from pharmacotherapy lifestyle modifications to implantable cardioverter-defibrillators transplantation refractory cases. Main body Anthracyclines, particularly doxorubicin, have emerged as crucial components cancer treatment, demonstrating significant antitumor activity across malignancies. These drugs become standard numerous chemotherapy regimens, improving patient outcomes. However, their use severe cardiotoxicity, failure. The mechanisms anthracycline action toxicity are complex, involving DNA damage, iron-mediated free radical production, disruption cardiovascular homeostasis. Doxorubicin-induced (DIC) complication treatment poor prognosis limited effective treatments. pathophysiology DIC multiple mechanisms, oxidative stress, inflammation, mitochondrial calcium homeostasis disorder. Despite extensive research, no for established currently available. Dexrazoxane only FDA-approved protective agent, but it has limitations. Recent studies explored potential therapeutic approaches, natural drugs, endogenous substances, new dosage forms, herbal medicines. lack experimental models incorporating pre-existing limits understanding efficacy. Conclusion Cardiomyopathy, whether secondary, poses clinical challenge due its varying etiologies advanced stages. Anthracycline-induced chemotherapy, doxorubicin being notable contributor. advancements therapies, cardiotoxic effects anthracyclines necessitate further investigation preventive strategies interventions improve

Язык: Английский

Toll-like Receptor 4 Inflammatory Perspective on Doxorubicin-Induced Cardiotoxicity DOI Creative Commons
Natticha Sumneang, Pongpan Tanajak,

Thura Tun Oo

и другие.

Molecules, Год журнала: 2023, Номер 28(11), С. 4294 - 4294

Опубликована: Май 24, 2023

Doxorubicin (Dox) is one of the most frequently used chemotherapeutic drugs in a variety cancers, but Dox-induced cardiotoxicity diminishes its therapeutic efficacy. The underlying mechanisms are still not fully understood. More significantly, there no established guidelines for cardiotoxicity. To date, cardiac inflammation widely considered as involved Toll-like receptor 4 (TLR4) signaling pathway plays key role inflammation, and growing evidence reports that TLR4-induced strongly linked to In this review, we outline address all available demonstrating involvement TLR4 different models This review also discusses effect on Understanding might be beneficial developing potential strategy

Язык: Английский

Процитировано

20
Irisin protects against doxorubicin-induced cardiotoxicity by improving AMPK-Nrf2 dependent mitochondrial fusion and strengthening endogenous anti-oxidant defense mechanisms DOI

Caili Zhuo,

Juan-Juan Xin,

Wenjing Huang

и другие.

Toxicology, Год журнала: 2023, Номер 494, С. 153597 - 153597

Опубликована: Июль 25, 2023

Язык: Английский

Процитировано

19
NOX4 aggravates doxorubicin-induced cardiomyocyte pyroptosis by increasing reactive oxygen species content and activating the NLRP3 inflammasome DOI Open Access
Hong Zeng,

Pengtao Zou,

Yanmei Chen

и другие.

Cardiovascular Diagnosis and Therapy, Год журнала: 2024, Номер 14(1), С. 84 - 100

Опубликована: Фев. 1, 2024

Background: Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)-mediated reactive oxygen species (ROS) has been reported to induce cardiomyocyte apoptosis, but its effect on pyroptosis of cardiomyocytes rarely reported. This paper aimed explore the effects NOX4-mediated ROS production doxorubicin (DOX)-induced myocardial injury and through nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. Methods: HL-1 cells were treated with DOX or mice (30 divided into five groups six mice/group) underwent intraperitoneal injection (5 mg/kg, once a week, times) injury, followed by assessment NOX4 NLRP3 expression in cell supernatant tissues. In cells, proliferation was tested MTT assay activity probes. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, glutathione (GSH) evaluated kits. proteins assessed western blotting. Subsequently, altered determine pyroptosis. animal models utilized evaluate changes cardiac function using an echocardiographic system, these parameters measured including left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-diastolic diameter (LVEDD). Furthermore, content markers determined mice. Results: treatment led pyroptosis, as evidenced weakened LVEF, LVFS, (P<0.05), elevated LVEDD, ROS, MDA increased decreased SOD GSH (P<0.05). Additionally, highly-expressed (P<0.05) DOX-induced overexpression intensified levels aggravate which reversed scavenger N-acetyl-cysteine. it revealed that combination short hairpin RNA (sh)-NOX4 overexpressed (oe)-NLRP3 cardioprotective sh-NOX4 tissue vitro vivo. No died during experiments, only two ruled out due weight loss greater than 20%. Conclusions: activated inflammasome, thereby aggravating

Язык: Английский

Процитировано

6
The mechanism and therapeutic strategies in Doxorubicin induced cardiotoxicity: Role of programmed cell death DOI Creative Commons
Yanzhao Li, Jing Yan, Pingzhen Yang

и другие.

Cell Stress and Chaperones, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

6
Simvastatin Reduces Doxorubicin-Induced Cardiotoxicity: Effects beyond Its Antioxidant Activity DOI Open Access

Michela Pecoraro,

Stefania Marzocco, Raffaella Belvedere

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7573 - 7573

Опубликована: Апрель 20, 2023

This study aimed to evaluate if Simvastatin can reduce, and/or prevent, Doxorubicin (Doxo)-induced cardiotoxicity. H9c2 cells were treated with (10 µM) for 4 h and then Doxo (1 was added, the effects on oxidative stress, calcium homeostasis, apoptosis evaluated after 20 h. Furthermore, we of co-treatment Connexin 43 (Cx43) expression localization, since this transmembrane protein forming gap junctions is widely involved in cardioprotection. Cytofluorimetric analysis showed that significantly reduced Doxo-induced cytosolic mitochondrial ROS overproduction, apoptosis, cytochrome c release. Spectrofluorimetric performed by means Fura2 levels stored mitochondria restored storage. Western blot, immunofluorescence, cytofluorimetric analyses Cx43 over-expression increased membrane phosphorylated Ser368. We hypothesized could justify consequent induction observed co-treated cells. Moreover, Ser368, which responsible closed conformational state junction, let us hypothesize leads cell-to-cell communication interruption block propagation harmful stimuli. Based these results, conclude be a good adjuvant anticancer therapy. Indeed, confirmed its antioxidant antiapoptotic activity, and, above all, highlighted interferes cellular localization

Язык: Английский

Процитировано

15
Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats DOI Creative Commons
Sara Gomes Espírito Santo, Marina Gaiato Monte, Bertha Furlan Polegato

и другие.

Molecules, Год журнала: 2023, Номер 28(7), С. 3004 - 3004

Опубликована: Март 28, 2023

Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX highly effective, its side effects are limiting factors, such cardio, nephro and hepatotoxicity. As such, approaches to mitigate these adverse encouraged. Omega 3 (ω-3), which class of long-chain polyunsaturated fatty acids, has been shown have anti-inflammatory antioxidant in preclinical bioassays. Thus, we evaluated the protective ω-3 supplementation on hepatotoxicity nephrotoxicity induced by multiple administrations rodents. Male Wistar rats (10 rats/group) were treated daily with (400 mg/kg/day) gavage six weeks. Two weeks after first administration, received (3.5 mg/kg, intraperitoneal, 1×/week) four treatment reduced body weight gain increased systemic genotoxicity caused liver-related (increase serum ALT levels, thickness Glisson's capsule, compensatory proliferation p65 levels) kidney-related urea creatinine incidence tubular dilatation) deleterious outcomes. In contrast, was safe abrogated DOX-related enhancement genotoxicity, levels. Furthermore, intervention 50% kidney histological lesions while reducing 40-50% protein level, proliferative response liver DOX. Our findings indicate that attenuated DOX-induced kidney. Therefore, our may inspire future mechanistical investigations clinical interventions reported

Язык: Английский

Процитировано

14
Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against doxorubicin-induced cardiotoxicity DOI Open Access
Thais Peclat, Guillermo Agorrody,

Laura Colman

и другие.

Cardiovascular Research, Год журнала: 2024, Номер 120(3), С. 286 - 300

Опубликована: Янв. 25, 2024

Abstract Aims Doxorubicin (DXR) is a chemotherapeutic agent that causes dose-dependent cardiotoxicity. Recently, it has been proposed the NADase CD38 may play role in doxorubicin-induced cardiotoxicity (DIC). main NAD+-catabolizing enzyme mammalian tissues. Interestingly, heart, mostly expressed as an ecto-enzyme can be targeted by specific inhibitory antibodies. The goal of present study to characterize ecto-enzymatic activity cardiac metabolism and development DIC. Methods results Using both transgenic animal model non-cytotoxic enzymatic anti-CD38 antibody, we investigated its ecto-NADase DIC pre-clinical models. First, observed was prevented catalytically inactive (CD38-CI) mice. Both left ventricular systolic function exercise capacity were decreased wild-type but not CD38-CI mice treated with DXR. Second, blocking CD38-NADase antibody 68 (Ab68) likewise protected against DXR-related mortality 50%. A reduction DXR-induced mitochondrial dysfunction, energy deficiency, inflammation gene expression identified mechanisms mediating protective effects. Conclusion NAD+-preserving strategies inactivation via genetic or pharmacological-based approach improve energetics reduce dysfunction otherwise seen acute DXR model.

Язык: Английский

Процитировано

5
Cardioprotective potentials of myricetin on doxorubicin-induced cardiotoxicity based on biochemical and transcriptomic analysis DOI Open Access

Jaili Li,

Ting Luo, Yao Zhao

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116748 - 116748

Опубликована: Май 21, 2024

Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX constrained by its cardiotoxicity. Myricetin (MYR) natural flavonoid widely present many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects mechanisms alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected 15 mg/kg to establish the DIC, MYR solutions administrated gavage investigate cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics RT-qPCR elucidate potential mechanism DIC treatment. reduced cardiac injury produced DOX, decreased levels cTnI, AST, LDH, BNP, improved myocardial fibrosis. effectively prevented oxidative stress, such as lowered MDA elevated SOD, CAT, GSH activities. suppressed NLRP3 ASC gene expression inhibit pyroptosis while regulating Caspase1 Bax reduce cell apoptosis. According transcriptomic glucose fatty acid metabolism associated differential expression. KEGG pathway analysis revealed enrichment PPAR AMPK pathways, among others. Following validation, was found alleviate glycolipid pathway-related genes. Our findings demonstrated that could mitigate processes apoptosis, pyroptosis. critical improving energy abnormalities mediated signaling pathway. In conclusion, holds promise therapeutic strategy for DIC.

Язык: Английский

Процитировано

5
Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis DOI Creative Commons
Jianmei Chen, Shuo Qiu, Yang Liu

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 2, 2024

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), thus limits use doxorubicin (DOX) clinic. Here, we further showed that cardiac ferroptosis induced DOX mice was attributed to up-regulation Hmox1, as knockdown Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed ultrasound microbubble destruction (UTMD) heart region. UTMD greatly facilitated exosome heart. Consistently, assisted exosomal siHomox1 nearly blocked subsequent cardiotoxicity doxorubicin. In summary, our findings reveal upregulation HMOX1 induces cardiomyocytes UTMD-assisted siHmox1 can be used potential therapeutic strategy for DIC.

Язык: Английский

Процитировано

5
Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots DOI Creative Commons
Rui Zhang, Xingyu Lin, Rongjie Lin

и другие.

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 29, 2025

Overproduction of reactive oxygen species (ROS), elevated synovial inflammation, hyperplasia and fibrosis are the main characteristic microenvironment in rheumatoid arthritis (RA). Macrophages fibroblast-like synoviocytes (FLSs) play crucial roles progression RA. Hence, synergistic combination ROS scavenging, macrophage polarization from pro-inflammatory M1 phenotype towards M2 anti-inflammatory phenotype, restoring homeostasis FLSs will provide a promising therapeutic strategy for In this study, we successfully synthesized metformin-derived carbon dots (MCDs), investigated antirheumatic effect vivo vitro. Designed MCDs could target inflamed cells accumulate at inflammatory joints collagen-induced (CIA) rats. investigation suggested that reduced inflammation hyperplasia, ultimately prevented cartilage destruction, bone erosion, CIA addition, eliminated cellular macrophages RA through enzyme-like catalytic activity as well inhibiting NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, effectively polarizing them into to realize effect. Furthermore, inhibit proliferation, migration, FLSs. Mechanistically, restored while reducing level by blocking IL-6/gp130 pathway. Combined with preferable biocompatibility, offer prospective treatment approach

Язык: Английский

Процитировано

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