Pinocembrin inhibited cardiomyocyte pyroptosis against doxorubicin-induced cardiac dysfunction via regulating Nrf2/Sirt3 signaling pathway

Gu, Jiwei; Huang, Hui; Liu, Chunlian; Jiang, Bo; Li, Mingliang; Liu, Li; Zhang, Shuya

doi:10.1016/j.intimp.2021.107533

Cited by 48 publications

(35 citation statements)

References 36 publications

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“…The pathways that regulate Nrf2 signaling were thought to play a fundamental role in the pathogenesis of doxorubicin-induced cardiotoxicity [26]. Doxorubicin was proven to decrease Nrf2 content in cardiac tissues with subsequent increase in the generation of free radicals and ROS in cardiomyocytes, which subsequently impair myocardial functions [27].…”

Section: Discussionmentioning

confidence: 99%

Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity

Kabel

Salama

Adwas³

et al. 2021

Pharmaceuticals

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Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin on doxorubicin-induced cardiac dysfunction in rats. In a model of doxorubicin-induced cardiotoxicity, the effects of different doses of fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes. Fraxetin, in a dose-dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and inflammation on myocardial muscles with significant decrease in NLRP3 inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition, fraxetin, in a dose-dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by doxorubicin in cardiomyocytes. As a result, fraxetin may be put into consideration as a new adjuvant line of therapy on the way to mitigate doxorubicin-induced cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity

Kabel

Salama

Adwas³

et al. 2021

Pharmaceuticals

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“…Fibrosis is initiated by the presence of injurious agents that cause the destruction of parenchymal cells through necrosis, apoptosis, pyroptosis, necroptosis, and ferroptosis [ 5 , 6 , 7 , 8 , 9 ]. This tissular damage is accompanied by the activation of the inflammatory response and the arrival of several types of blood cells to the injury.…”

Section: Introductionmentioning

confidence: 99%

Is the Macrophage Phenotype Determinant for Fibrosis Development?

et al. 2021

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Fibrosis is a pathophysiological process of wound repair that leads to the deposit of connective tissue in the extracellular matrix. This complication is mainly associated with different pathologies affecting several organs such as lung, liver, heart, kidney, and intestine. In this fibrotic process, macrophages play an important role since they can modulate fibrosis due to their high plasticity, being able to adopt different phenotypes depending on the microenvironment in which they are found. In this review, we will try to discuss whether the macrophage phenotype exerts a pivotal role in the fibrosis development in the most important fibrotic scenarios.

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“…Furthermore, elevated cardiac and serological biomarkers in the doxorubicin-treated rats were greatly reduced when propolis was simultaneously administered (24). A study on reducing the toxicity of doxorubicin with pinocembrin, a avonoid containing propolis, showed similar results, normalizing the cardiac biomarkers (52). Regarding the AST/ALT ratio, which was almost doubled in our study in the 5-FU group compared to the Control group, there is growing evidence supporting this hypothesis that AST/ALT ratio would increase in cardiac events, especially ST-elevation MI (STEMI) (53,54).…”

Section: Discussionmentioning

confidence: 86%

The effect of propolis on 5-fluorouracil-induced cardiac toxicity in rats

Barary

Hosseinzadeh

Liang

et al. 2022

Preprint

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Background 5- Fluorouracil (5-FU) is one of the most common chemotherapeutic agents used in treating solid tumors, and the 5-FU-induced cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs. Propolis (Pro) has vigorous anti-inflammatory activity. Its cardio-protective characteristic against doxorubicin-induced cardiotoxicity was previously proven. The current study aimed to appraise the effect of Pro on 5-FU-induced cardiotoxicity in rats. Methods Twenty-four male Wistar rats were divided into four groups: Control, 5-FU, 5-FU + Pro 250 mg/kg, and 5-FU + Colchicine (CLC) 5 mg/kg. Different hematological, serological, biochemical, histopathological, and molecular assays were performed to assess the study aim. Moreover, rat myocardium (H9C2(2 − 1)) and human skin fibroblast (HNFF-P18) cell lines were also used to assess this protective effect in-vitro. Results 5-FU resulted in significant cardiotoxicity represented by an increase in malondialdehyde (MDA) levels, cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) expression, cardiac enzyme levels, and histopathological degenerations. 5-FU treatment also decreased bodyweight, total anti-oxidant capacity (TAC), catalase (CAT) levels, blood cell counts, and hemoglobin (Hb) levels. In addition, 5-FU disrupted ECG parameters, including increased elevation in the ST-segment and increased QRS complex and QTc duration. Treating with Pro reduced oxidative stress, cardiac enzymes, histopathological degenerations, and COX-2 expression in cardiac tissue alleviated ECG disturbances and increased the number of blood cells and TAC levels. Moreover, 5-FU-induced bodyweight loss was ameliorated after treatment with Pro. Conclusion Our results demonstrated that treatment with Pro significantly improved cardiotoxicity induced by 5-FU in rats.

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Pinocembrin inhibited cardiomyocyte pyroptosis against doxorubicin-induced cardiac dysfunction via regulating Nrf2/Sirt3 signaling pathway

Cited by 48 publications

References 36 publications

Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity

Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity

Is the Macrophage Phenotype Determinant for Fibrosis Development?

The effect of propolis on 5-fluorouracil-induced cardiac toxicity in rats

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