Compound Danshen Dripping Pill inhibits doxorubicin or isoproterenol-induced cardiotoxicity
TL;DR: CDDP can protect against myocardial injuries in different models, suggesting its potential application for HF treatment, and shows that CDDP cannot protect against oxygen-glucose deprivation-induced injuries.
About: This article is published in Biomedicine & Pharmacotherapy.The article was published on 2021-06-01 and is currently open access. It has received 9 citations till now. The article focuses on the topics: Cardiotoxicity.
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TL;DR: In this paper, the authors provided a detailed review on the current understanding of the pathological mechanisms behind the well-known Dox-induced cardiotoxicity and provided some of the most plausible pharmacological strategies which have been tested against doxorubicin-induced Cardiotoxicity.
172 citations
TL;DR: The related mechanisms of DOX-induced cardiac mitochondrial bioenergetics disorders reported in recent years are summarized, including mitochondrial substrate metabolism, the mitochondrial respiratory chain, myocardial ATP storage and utilization, and other mechanisms affecting mitochondrial bioenersgetics.
Abstract: Doxorubicin (DOX) is an anthracycline chemotherapy drug, which is indispensable in antitumor therapy. However, its subsequent induction of cardiovascular disease (CVD) has become the primary cause of mortality in cancer survivors. Accumulating evidence has demonstrated that cardiac mitochondrial bioenergetics changes have become a significant marker for doxorubicin-induced cardiotoxicity (DIC). Here, we mainly summarize the related mechanisms of DOX-induced cardiac mitochondrial bioenergetics disorders reported in recent years, including mitochondrial substrate metabolism, the mitochondrial respiratory chain, myocardial ATP storage and utilization, and other mechanisms affecting mitochondrial bioenergetics. In addition, intervention for DOX-induced cardiac mitochondrial bioenergetics disorders using chemical drugs and traditional herbal medicine is also summarized, which will provide a comprehensive process to study and develop more appropriate therapeutic strategies for DIC.
4 citations
TL;DR: It is demonstrated that DAI alleviates DOX-induced cardiotoxicity by regulating cardiac energy metabolism as well as reducing inflammation, oxidative stress, apoptosis and fibrosis, indicating its potential application for HF treatment.
Abstract: Heart failure (HF) is a clinical syndrome characterized by typical symptoms that usually occur at the end stage of various heart diseases and lead to death. Daidzein (DAI), an isoflavone found in soy foods, is widely used to treat menopausal syndrome, prostate cancer, breast cancer, heart disease, cardiovascular disease, and osteoporosis, and has anti-oxidant and anti-inflammatory properties. However, the effects of DAI in HF remain unknown. In this study, doxorubicin (DOX) was used to establish HF models of C57BL/6J mice and H9c2 cells with DAI treatment. Our results showed that DAI markedly improved the DOX-induced decline in cardiac function, and decreased the left ventricular ejection fraction, cardiac inflammation, oxidative stress, apoptosis, and fibrosis. Mechanistically, DAI affects cardiac energy metabolism by regulating SIRT3, and meets the ATP demand of the heart by improving glucose, lipid, and ketone body metabolism as well as restoring mitochondrial dysfunction in vivo and in vitro. Additionally, DAI can exert an antioxidant function and alleviate HF through the SIRT3/FOXO3a pathway. In conclusion, we demonstrate that DAI alleviates DOX-induced cardiotoxicity by regulating cardiac energy metabolism as well as reducing inflammation, oxidative stress, apoptosis and fibrosis, indicating its potential application for HF treatment.
4 citations
TL;DR: The findings illustrated for the first time that the E3 ubiquitination ligase protein RNF181 may serve as a potential biomarker in CAD, but further in vivo validation is warranted.
Abstract: Background: Coronary artery disease (CAD) exerts a global challenge to public health. Genetic heritability is one of the most vital contributing factors in the pathophysiology of CAD. Co-expression network analysis is an applicable and robust method for the interpretation of biological interaction from microarray data. Previous CAD studies have focused on peripheral blood samples since the processes of CAD may vary from tissue to blood. It is therefore necessary to find biomarkers for CAD in heart tissues; their association also requires further illustration. Materials and Methods: To filter for causal genes, an analysis of microarray expression profiles, GSE12504 and GSE22253, was performed with weighted gene co-expression network analysis (WGCNA). Co-expression modules were constructed after batch effect removal and data normalization. The results showed that 7 co-expression modules with 8,525 genes and 1,210 differentially expressed genes (DEGs) were identified. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Four major pathways in CAD tissue and hub genes were addressed in the Hybrid Mouse Diversity Panel (HMDP) and Human Protein Atlas (HPA), and isoproterenol (ISO)/doxycycline (DOX)-induced heart toxicity models were used to validate the hub genes. Lastly, the hub genes and risk variants were verified in the CAD cohort and in genome-wide association studies (GWAS). Results: The results showed that RNF181 and eight other hub genes are perturbed during CAD in heart tissues. Additionally, the expression of RNF181 was validated using RT-PCR and immunohistochemistry (IHC) staining in two cardiotoxicity mouse models. The association was further verified in the CAD patient cohort and in GWAS. Conclusion: Our findings illustrated for the first time that the E3 ubiquitination ligase protein RNF181 may serve as a potential biomarker in CAD, but further in vivo validation is warranted.
2 citations
TL;DR: Wang et al. as mentioned in this paper reviewed the effects and molecular mechanisms of traditional Chinese medicine on chemoradiotherapy-related cardiotoxicity and concluded that traditional Chinese Medicine can mitigate cancer-related Cardiotoxicity via various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism.
Abstract: Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.
1 citations
References
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Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
TL;DR: 2 well-known clinical concepts of myocardial glucose metabolism require critical reevaluation: the diagnostic concept of metabolic imaging with PET and the glucose tracer analogue 18F-2-deoxy- 2-fluoro-d-glucose (FDG) and the therapeutic concept of metabolism support for the postischemic heart with glucose, insulin, and K+ (GIK).
Abstract: The homeostasis of plasma glucose levels is essential for survival of the mammalian organism. Since blood glucose concentration is maintained within a narrow range, glucose is a most reliable substrate for energy production in the heart. The importance of glucose metabolism via glycolysis is well appreciated in ischemic and hypertrophied heart muscle,1 2 3 4 but aerobic glucose metabolism for support of normal contractile function has received less attention, mainly because of the well-known fact that fatty acids are normally the predominant fuel for cardiac energy production.2 5 6 We have drawn attention to the heart as a true “omnivore,” ie, an organ that functions best when it oxidizes different substrates simultaneously.7 In light of this concept, we wish to reexamine myocardial glucose metabolism and its relevance to the human heart. In recent years, the tools of molecular and cellular biology have provided new insight into the mechanisms of glucose transport and phosphorylation. Glycogen metabolism has come into greater focus. The regulation of glycolysis is more accurately defined, and the effects of second messengers on myocardial glucose utilization are better known. In view of this background, 2 well-known clinical concepts of myocardial glucose metabolism require critical reevaluation: (1) the diagnostic concept of metabolic imaging with PET and the glucose tracer analogue 18F-2-deoxy-2-fluoro-d-glucose (FDG) and (2) the therapeutic concept of metabolic support for the postischemic heart with glucose, insulin, and K+ (GIK).
The simple sugar d-glucose is the most abundant organic molecule in nature. Glucose for the heart is derived either from the bloodstream or from intracellular stores of glycogen (Figure 1⇓). The transport of glucose into the cardiomyocyte occurs along a steep concentration gradient and is regulated by specific transporters. Intracellular glucose is rapidly phosphorylated and becomes a substrate for the …
405 citations
TL;DR: It is concluded that Coronin 1B's coordination of filament formation by Arp2/3 complex and filament turnover by Cofilin is required for effective lamellipodial protrusion and cell migration.
218 citations
TL;DR: The present review addresses the effects of indirect and direct modulators of fatty acid (FA) oxidation, which are the best pharmacological agents available to date for 'metabolic therapy' of failing hearts.
Abstract: In the advanced stages of heart failure, many key enzymes involved in myocardial energy substrate metabolism display various degrees of down-regulation. The net effect of the altered metabolic phenotype consists of reduced cardiac fatty oxidation, increased glycolysis and glucose oxidation, and rigidity of the metabolic response to changes in workload. Is this metabolic shift an adaptive mechanism that protects the heart or a maladaptive process that accelerates structural and functional derangement? The question remains open; however, the metabolic remodelling of the failing heart has induced a number of investigators to test the hypothesis that pharmacological modulation of myocardial substrate utilization might prove therapeutically advantageous. The present review addresses the effects of indirect and direct modulators of fatty acid (FA) oxidation, which are the best pharmacological agents available to date for ‘metabolic therapy’ of failing hearts. Evidence for the efficacy of therapeutic strategies based on modulators of FA metabolism is mixed, pointing to the possibility that the molecular/biochemical alterations induced by these pharmacological agents are more complex than originally thought. Much remains to be understood; however, the beneficial effects of molecules such as perhexiline and trimetazidine in small clinical trials indicate that this promising therapeutic strategy is worthy of further pursuit.
217 citations