Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107281 - 107281

Published: June 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.

Language: Английский

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The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4654 - 4654

Published: April 25, 2024

The supply and control of iron is essential for all cells vital many physiological processes. All functions activities are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin chelator–iron complexes haem play major roles metabolism human physiology. Similarly, the mainstay treatments most common diseases metabolism, namely deficiency anaemia overload, involve iron–chelator iron-chelating drugs deferiprone (L1), deferoxamine (DF) deferasirox. Endogenous citric acid glutathione exogenous ascorbic also important homeostasis. Recent advances treatment effective ferric tri-maltol complex (feraccru or accrufer) transfusional overload using L1 L1/DF combinations have decreased associated mortality morbidity improved quality life millions patients. Many other chelating ciclopirox, dexrazoxane EDTA used daily by patients diseases. their metabolites iron-chelation capacity hydroxyurea, tetracyclines, anthracyclines aspirin, well dietary molecules gallic acid, caffeic quercetin, ellagic maltol phytochelators, known to interact affect related Different interactions observed presence essential, xenobiotic, diagnostic theranostic metal ions competing iron. Clinical trials Parkinson’s, Alzheimer’s neurodegenerative diseases, HIV infections, cancer, diabetic nephropathy inflammation, highlight importance chelation therapy clinical conditions. proposed use modulating ferroptosis signifies a new era design therapeutic strategies introduction artificial intelligence guidance optimal outcomes personalised medicine expected increase further impact medicine, survival metabolic disorders

Language: Английский

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Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 471, P. 134389 - 134389

Published: April 23, 2024

Language: Английский

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Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 2, 2024

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), thus limits use doxorubicin (DOX) clinic. Here, we further showed that cardiac ferroptosis induced DOX mice was attributed to up-regulation Hmox1, as knockdown Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed ultrasound microbubble destruction (UTMD) heart region. UTMD greatly facilitated exosome heart. Consistently, assisted exosomal siHomox1 nearly blocked subsequent cardiotoxicity doxorubicin. In summary, our findings reveal upregulation HMOX1 induces cardiomyocytes UTMD-assisted siHmox1 can be used potential therapeutic strategy for DIC.

Language: Английский

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Protective efficacy of Schizandrin B on ameliorating nephrolithiasis via regulating GSK3β/Nrf2 signaling-mediated ferroptosis in vivo and in vitro

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 117, P. 110042 - 110042

Published: March 20, 2023

Language: Английский

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Ferroptosis and Senescence: A Systematic Review

Published: Jan. 17, 2023

Background: Senescence is a cellular ageing process in all multicellular organisms. It characterized by decline functions and proliferation, resulting increased damage death. This condition plays an essential role the significantly contributes to development of age-related complications. On other hand, ferroptosis systemic cell death excessive iron accumulation followed generation reactive oxygen species (ROS). Oxidative stress common trigger this may be induced various factors such as toxins, drugs, inflammation. Ferroptosis linked numerous illnesses, including cardiovascular disease, neurodegeneration, cancer. Relevance these conditions disease: believed contribute tissue organ function that occurs with ageing. has also been pathologies, diseases, diabetes, In particular, senescent cells have shown produce inflammatory cytokines pro-inflammatory molecules can conditions. health disorders, cancer [1]. known play developing diseases promoting damaged or diseased contributing inflammation often associated them. Both senescence are complex processes still not fully understood. Further research needed thoroughly understand identify potential interventions target prevent treat Objectives: systematic review aims assess mechanisms underlying link connecting senescence, ferroptosis, ageing, disease.

Language: Английский

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Targeting the ferroptosis crosstalk: novel alternative strategies for the treatment of major depressive disorder

General Psychiatry, Journal Year: 2023, Volume and Issue: 36(5), P. e101072 - e101072

Published: Oct. 1, 2023

Depression is a major contributor to poor global health and disability, with recently increasing incidence. Although drug therapy commonly used treat depression, conventional antidepressant drugs have several disadvantages, including slow onset, low response rates severe adverse effects. Therefore, developing effective therapies for depression remains challenging. various aetiological theories of exist, the underlying mechanisms are complex, further research crucial. Moreover, oxidative stress (OS)-induced lipid peroxidation has been demonstrated trigger ferroptosis. Both OS ferroptosis pivotal implicated in pathogenesis neurological disorders, investigation mediators involved these processes emerged as prominent active direction. One previous study revealed that regulatory proteins could reverse depressive symptoms by inhibiting vivo , suggesting an important role depression. Hence, our current comprehensive review offers up-to-date perspective on intricate involved, specifically concerning context along promising prospects using molecular target We delineate key targets most notably reactive oxygen species iron overload. Considering OS-induced delving deeper into subsequent will contribute significantly identification novel therapeutic

Language: Английский

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The mechanism and therapeutic strategies in Doxorubicin induced cardiotoxicity: Role of programmed cell death

Cell Stress and Chaperones, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13990 - 13990

Published: Nov. 13, 2022

There is new and increasing evidence from in vitro, vivo clinical studies implicating the pivotal role of iron associated metabolic pathways initiation, progression development cancer metastasis. New toxicity mechanisms pathways, as well genomic, transcription other factors, have been linked to many are related iron. Accordingly, a number targets for chelators identified characterized anticancer strategies, addition classical restriction of/reduction supply, inhibition transferrin delivery, ribonucleotide reductase DNA synthesis high antioxidant potential. The include removal excess iron-laden macrophages, which affects activity; modulation ferroptosis; ferritin control hyperferritinemia; hypoxia hypoxia-inducible factor (HIF); function molecular species such STEAP4 metalloreductase metastasis suppressor N-MYC downstream-regulated gene-1 (NDRG1); oxidative stress damage affecting mitochondrial function, etc. Many these new, but also previously known appear affect all stages cancer, drug resistance. Iron-chelating drugs especially deferiprone (L1), has shown recent fulfill multi-target above targets, proposed phase II trials patients. In contrast, lipophilic their complexes induction ferroptosis some refractory or recurring tumors resistance where effective treatments absent. need readdress therapy therapeutic strategies targeting multifactorial processes, including application multi-targeting involving iron-chelator complexes. protocols combinations with L1 chelating could increase activity, decrease metastasis, improve treatments, reduce overall survival

Language: Английский

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The Role of Selenium in Atherosclerosis Development, Progression, Prevention and Treatment

Biomedicines, Journal Year: 2023, Volume and Issue: 11(7), P. 2010 - 2010

Published: July 17, 2023

Selenium is an essential trace element that for various metabolic processes, protection from oxidative stress and proper functioning of the cardiovascular system. Se deficiency has long been associated with multiple diseases, including endemic Keshan’s disease, common heart failure, coronary myocardial infarction atherosclerosis. Through selenoenzymes selenoproteins, involved in numerous crucial such as redox homeostasis regulation, stress, calcium flux thyroid hormone metabolism; unbalanced supply may disrupt these processes. In this review, we focus on importance health provide updated information role specific processes development pathogenesis atherosclerosis (oxidative inflammation, endothelial dysfunction, vascular calcification cell apoptosis). We also discuss recent randomised trials investigating supplementation a potential therapeutic preventive agent treatment.

Language: Английский

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