Dataset Information

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3.

ABSTRACT: Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce inflammation, oxidative stress, and apoptosis in various diseases. This study was designed to investigate the role of TBM in DOX-induced cardiotoxicity and uncover the underlying mechanisms. H9c2 cell line and C57BL/6 mice were used to construct an in vitro and in vivo model of DOX-induced myocardial injury, respectively. We observed that DOX treatment provoked inflammation, oxidative stress, and cardiomyocyte apoptosis, which were significantly alleviated by TBM administration. Mechanistically, TBM attenuated DOX-induced downregulation of sirtuin 3 (SIRT3), and SIRT3 inhibition abrogated the beneficial effects of TBM both in vitro and in vivo. In conclusion, TBM eased inflammation, oxidative stress, and apoptosis in DOX-induced cardiotoxicity by increasing the expression of SIRT3, suggesting that it holds great promise for treating DOX-induced cardiac injury.

SUBMITTER: Zhang W

PROVIDER: S-EPMC9867588 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3.

Zhang Wei W Fan Zhixing Z Wang Fengyuan F Yin Lin L Wu Jinchun J Li Dengke D Song Siwei S Wang Xi X Tang Yanhong Y Huang Congxin C

Oxidative medicine and cellular longevity 20230114

Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce inflammation, oxidative stress, and apoptosis in various diseases. This study was designed to investigate the role of TBM in DOX-induced cardiotoxicity and uncover the underlying mechanisms. H9c2 cell line and C57BL/6 mice were used to construct an in vitro an ...[more]

PMID: 36691640

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Project description:Doxorubicin (DOX) is a potent anticancer drug with adverse cardiotoxic effects. Alginates are multifunctional biopolymers and polyelectrolytes derived from the cell walls of brown seaweeds. They are nontoxic, biocompatible, and biodegradable, and hence, utilized in several biomedical and pharmaceutical applications. Here, we investigated the potential cardioprotective effect of thermally treated sodium alginate (TTSA), which was extracted and purified from the seaweed Sargassum aquifolium, in treating acute DOX cardiotoxicity and apoptotic pathways in rats. UV-visible spectroscopy, Fourier-transform infrared, and nuclear magnetic resonance (1H-NMR) spectroscopy techniques were used to characterize TTSA. CK-MB and AST levels in sera samples were determined. The expression levels of Erk-2 (MAPK-1) and iNOS genes were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Erk-2, anti-apoptotic p53, and caspase-3 were analyzed using western blotting and ELISA. For the in vivo studies, sixty rats were randomly divided equally into six groups and treated with DOX, followed by TTSA. We revealed that treatment with TTSA, which has low molecular weight and enhanced antioxidant properties, improved DOX-mediated cardiac dysfunction and alleviated DOX-induced myocardial apoptosis. Furthermore, TTSA exhibited a cardioprotective effect against DOX-induced cardiac toxicity, indicated by the increased expression of MAPK-1 (Erk2) and iNOS genes, which are implicated in the adaptive responses regulating DOX-induced myocardial damage. Moreover, TTSA significantly (p < 0.05) suppressed caspase-3 and upregulated anti-apoptotic protein p53 expression. TTSA also rebalanced the cardiomyocyte redox potential by significantly (p < 0.05) increasing the levels of endogenous antioxidant enzymes, including catalase and superoxide dismutase. Our findings suggest that TTSA, particularly at a dose of 400 mg/kg b.w., is a potential prophylactic supplement for treating acute DOX-linked cardiotoxicity.

Project description:Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Dataset Information

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3.

Publications

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3.

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