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

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156624 - 156624

Published: March 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.

Language: Английский

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Betaine ameliorates doxorubicin‐induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF‐β expression

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(8), P. 4134 - 4147

Published: April 23, 2024

Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to life-threatening side effects, such as cardiotoxicity. It evident that betaine anti-oxidant, and anti-inflammatory activity several beneficial decreasing the amyloid-β generation, reducing obesity, improving steatosis fibrosis, activating AMP-activated protein kinase (AMPK). However, whether could mitigate DOX-induced cardiomyopathy still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose cumulative of 20 mg/kg, i.p.). Further, (200 400 mg/kg) co-treated through oral gavage for 28 days. After completion study, biochemical, oxidative stress parameters, histopathology, western blotting, qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, triglyceride levels, which are associated increased also mitigated by intervention SOD, catalase, MDA, nitrite levels restored. The histopathological investigation confirmed cardioprotective effect against tissue injury reversed. molecular analysis revealed suppressed expression phospho-p53, phospho-p38 MAPK, NF-kB p65, PINK 1 an upregulation AMPK downregulation Nrf2 expression. Interestingly, experiments show alleviates increase inflammatory (TNF-α, NLRP3, IL-6) fibrosis (TGF-β Acta2) related gene expression, halting cardiac injury. improves mRNA Nrf2, thus modulating antioxidant proteins preventing damage. Here, we provide first evidence prevents inhibiting stress, inflammation, regulating AMPK/Nrf2/TGF-β We believe can be utilized potential novel therapeutic strategy

Language: Английский

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The mechanism and therapeutic strategies in Doxorubicin induced cardiotoxicity: Role of programmed cell death

Cell Stress and Chaperones, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117312 - 117312

Published: Aug. 20, 2024

Anthracyclines are broad-spectrum anticancer drugs, but their clinical use is limited due to severe cardiotoxicity. Anthracycline-induced cardiotoxicity (AIC) remains a significant cause of heart disease-related mortality in many cancer survivors. The underlying mechanisms AIC have been explored over the past few decades. Reactive oxygen species and drug-induced inhibition topoisomerase II beta well-studied mechanisms, with mitochondria being prominently investigated organelle. Emerging such as ferroptosis, Ca

Language: Английский

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A novel approach to the prevention and management of chemotherapy-induced cardiotoxicity: PANoptosis

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: 407, P. 111379 - 111379

Published: Jan. 8, 2025

Language: Английский

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The Role of Oxytocin Neurons in the Paraventricular Nucleus in Chronic-Sleep-Deprivation-Mediated Abnormal Cardiovascular Responses

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 220 - 220

Published: March 25, 2025

Sleep disorders increase the risk of cardiovascular diseases. However, underlying mechanisms remain unclear. This study aims to examine critical role oxytocin neurons in paraventricular nucleus (PVNOXT) regulating system and elucidate potential through which sleep disturbance may contribute In this study, using an automated deprivation system, mice were given chronic (cSD) for 7 days, 6 h per day. cSD induced blood transcriptomic alterations accompanied by lower heart rate, higher pressure, elevated cardiac autophagy/apoptosis. Instant optogenetic activation provoked rate suppression normal mice, whereas precipitated intermittent arrest. On contrary, inhibition PVNOXT showed no influence on but it attenuated cSD-induced rise pressure. Long-term low-frequency stimulation (LTF) decreased neuronal excitability release, effectively reversing cSD-mediated responses. Mechanistically, triggered upregulation blood-derived 3-mercaptopyruvate sulfurtransferase (mPST), a postsynaptic activity certain extent. The quick long-term decrease LTF could lead feedback mPST expression thus reverse Altogether, modulation mediate abnormalities without affecting mice. Our research provided targets key diseases associated with disorders.

Language: Английский

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Leucine zipper protein 1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 63, P. 117 - 128

Published: Oct. 7, 2023

Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) essential for development function cardiovascular system; however, its role in cardiac elusive.

Language: Английский

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Dual delivery of carbon monoxide and doxorubicin using haemoglobin–albumin cluster: proof of concept for well-tolerated cancer therapy

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(23), P. 5600 - 5608

Published: Jan. 1, 2024

The dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.

Language: Английский

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Liguzinediol potentiates the metabolic remodeling by activating the AMPK/SIRT3 pathway and represses Caspase-3/GSDME-mediated pyroptosis to ameliorate cardiotoxicity

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: June 14, 2024

Abstract Background Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, significant limitation in the clinical application of this widely used antineoplastic drug known its efficacy. This study aimed to explore effects and potential mechanisms underlying Lig’s protective role against DOX-induced cardiotoxicity. Methods C57BL/6 mice were treated with DOX. Cardiac function changes observed by echocardiography. structure HE Masson staining. Immunofluorescence was applied visualize cardiomyocyte apoptosis. Western blotting detect expression levels AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on cardiotoxicity mice. Results The results demonstrated effectively countered myocardial oxidative stress modulating intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD). reduced creatine (CK) lactate dehydrogenase (LDH), while ameliorating histopathological improving electrocardiogram profiles vivo. Furthermore, revealed activated AMPK/SIRT3 pathway, thereby enhancing mitochondrial attenuating cell In H9C2 cells DOX, co-administration AMPK inhibitor compound C (CC) led increase ROS levels. intervention reversed these effects, along downregulation GSDME-N, interleukin-1β (IL-1β), interleukin-6 (IL-6), suggesting Caspase-3/GSDME-mediated pyroptosis. Conclusion findings suggest alleviates through activation presenting itself natural product therapeutic preventing DOX-associated novel approach may pave way development alternative strategies management cardiac complications.

Language: Английский

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MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway

Redox Report, Journal Year: 2024, Volume and Issue: 30(1)

Published: Dec. 31, 2024

Inflammation and oxidative damage play critical roles in the pathogenesis of sepsis-induced cardiac dysfunction. Multiple EGF-like domains 9 (MEGF9) is essential for cell homeostasis; however, its role mechanism injury impairment remain unclear.

Language: Английский

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