Protective effects of esculetin against doxorubicin‐induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies

Journal of Biochemical and Molecular Toxicology, Год журнала: 2024, Номер 38(4)

Опубликована: Апрель 1, 2024

Abstract Doxorubicin (DOX) is widely used in cancer treatment but the dose‐related toxicity of DOX on organs including liver limit its use. Therefore, there great interest combining with natural compounds antioxidant properties to reduce and increase drug efficacy. Esculetin a coumarin derivative biological encompassing anti‐inflammatory activities. In light these properties, this study was meticulously crafted investigate potential esculetin preventing doxorubicin (DOX)‐induced hepatotoxicity Sprague‐Dawley rats. The rats were divided into total six groups: control group, group (administered at cumulative dose 5 mg/kg intraperitoneally every other day for 2 weeks), E50 50 day), E100 100 day) combined groups (DOX + E100) which administered together DOX. treatments, both alone combination E50, manifested reduction catalase (CAT mRNA) levels comparison group. Notably, enzymatic activities superoxide dismutase (SOD), CAT, glutathione peroxidase (GPx) witnessed significant decreases treated Moreover, induced statistically elevation malondialdehyde (MDA) levels, coupled concurrent decrease (GSH) levels. Additionally, molecular docking studies conducted. However, further are needed confirm hepatoprotective precisely elucidate mechanisms action.

Язык: Английский

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Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107281 - 107281

Опубликована: Июнь 26, 2024

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose major threat to human health. Cardiomyocytes low regenerative capacity, their death is key factor in the morbidity mortality of many CVDs. Cardiomyocyte can be regulated by specific signaling pathways known as programmed cell (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, ferroptosis, etc. Abnormalities PCD lead development variety cardiovascular diseases, there are also molecular-level interconnections between different under same disease model. Currently, link cardiomyocytes not fully understood. This review describes molecular mechanisms impact cardiomyocyte on development. Emphasis placed summary drugs potential therapeutic approaches that used treat targeting blocking cardiomyocytes.

Язык: Английский

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

Environmental Research, Год журнала: 2023, Номер 234, С. 116504 - 116504

Опубликована: Июнь 24, 2023

Язык: Английский

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AP39 through AMPK-ULK1-FUNDC1 pathway regulates mitophagy, inhibits pyroptosis, and improves doxorubicin-induced myocardial fibrosis

iScience, Год журнала: 2024, Номер 27(4), С. 109321 - 109321

Опубликована: Фев. 23, 2024

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether could improve doxorubicin-induced induced significant fibrosis while suppressing mitophagy-related proteins elevating pyroptosis-related proteins. Conversely, reverses these effects, enhancing mitophagy inhibiting pyroptosis. In vitro experiments revealed inhibited H9c2 cardiomyocyte pyroptosis, improved impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, upregulated AMPK-ULK1-FUNDC1 expression. contrast, AMPK inhibitor (dorsomorphin) ULK1 (SBI-0206965) reversed antagonism FUNDC1-mediated secondary These results suggest mitochondria-targeted can antagonize pyroptosis impaired in cardiomyocytes via remodeling.

Язык: Английский

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Redox Biology, Год журнала: 2024, Номер 76, С. 103321 - 103321

Опубликована: Авг. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Язык: Английский

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Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 179, С. 117312 - 117312

Опубликована: Авг. 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

Язык: Английский

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Dexmedetomidine Inhibits Ferroptosis Through the Akt/Gsk3β/Nrf2 Axis and Alleviates Adriamycin -Induced Cardiotoxicity

Опубликована: Янв. 1, 2025

Язык: Английский

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PCSK9 affects vascular senescence through the SIRT1 pathway

Experimental Gerontology, Год журнала: 2025, Номер 201, С. 112701 - 112701

Опубликована: Фев. 10, 2025

Язык: Английский

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Doxorubicin-Induced Cardiac Remodeling: Mechanisms and Mitigation Strategies

Cardiovascular Drugs and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Язык: Английский

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Amentoflavone protects against cisplatin-induced acute kidney injury by modulating Nrf2-mediated oxidative stress and ferroptosis and partially by activating Nrf2-dependent PANoptosis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 5, 2025

Cisplatin is a widely used drug for the treatment of solid organ cancer, but its renal toxicity cannot be ignored. Amentoflavone (AME), natural flavonoid compound, has remarkable pharmacological effects, including anti-inflammatory and antioxidative effects. The effect mechanism AME on cisplatin-induced acute kidney injury (CI-AKI) remain unclear. We investigated CI-AKI using HK-2 cell line C57BL/6 mice. Renal function, tissue damage, molecular markers were assessed to explore effects oxidative stress death pathways. In vitro, significantly suppressed cytotoxic cisplatin cells. Furthermore, inhibited ferroptosis PANoptosis (apoptosis, pyroptosis necroptosis). mice with induced by single intraperitoneal injection cisplatin, daily administration during AKI effectively improved function alleviated tubular injury, characterized normalization blood urea nitrogen (BUN) serum creatinine (SCr) levels; it also PANoptosis. antioxidant that activates Nrf2 pathway both in vivo vitro. knockout knockdown cells, protective against nephrotoxicity disappeared. However, after knockout, completely disappeared, partially via related Nrf2-dependent regulation

Язык: Английский

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