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

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 20, 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 AMPK, SIRT3, Caspase-3 GSDME. These experiments confirmed that had ameliorative effect on cardiotoxicity mice. Results The results demonstrated Lig effectively countered myocardial oxidative stress modulating intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD). reduced creatine kinase (CK), lactate dehydrogenase (LDH), ameliorated histopathological while improving electrocardiogram profiles vivo . Furthermore, revealed activated AMP-activated protein (AMPK)/sirtuin 3 (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 gasdermin E N-terminal fragment (GSDME-N), interleukin-1β (IL-1β), interleukin-6 (IL-6), suggesting Caspase-3/GSDME-mediated pyroptosis. Conclusions findings suggest alleviates through activation AMPK/SIRT3 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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Mechanisms of myocardial toxicity of antitumor drugs and potential therapeutic strategies: A review of the literature

Current Problems in Cardiology, Journal Year: 2024, Volume and Issue: 49(11), P. 102782 - 102782

Published: Aug. 10, 2024

With the successive development of chemotherapy drugs, good results have been achieved in clinical application. However, myocardial toxicity is biggest challenge. Anthracyclines, immune checkpoint inhibitors, and platinum drugs are widely used. Targeted drug delivery, nanomaterials dynamic imaging evaluation all emerging research directions. This article reviews recent literature on use targeted nanodrug delivery techniques to evaluate antineoplastic discusses potential mechanisms.

Language: Английский

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Polypeptide-Based Copper Ionophore for In Situ Glutathione-Triggered Chemodynamic and Chemotherapy

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Intracellular copper ion homeostasis has become an attractive target for cancer therapy. Herein, we report a 2,2'-dipicolylamine (DPA) functionalized polyglutamate derivative (PDHB) which is capable of rapidly forming PDHB-copper complex (PDHB@Cu) due to the strong coordination ability pendant DPA with Cu

Language: Английский

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