Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors

JACC CardioOncology, Год журнала: 2024, Номер 6(2), С. 159 - 182

Опубликована: Март 12, 2024

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally approved for type 2 diabetes mellitus, have demonstrated efficacy in reducing cardiovascular events, particularly heart failure, patients with and without diabetes. An intriguing research area involves exploring the potential application of SGLT2 inhibitors cardio-oncology, aiming to mitigate adverse events associated anticancer treatments. These present a unique dual nature, offering both cardioprotective effects properties, conferring double benefit cardio-oncology patients. In this review, authors first examine established failure subsequently explore existing body evidence, including preclinical clinical studies, that supports use context cardio-oncology. The further discuss mechanisms through which protect against toxicity secondary cancer treatment. Finally, they along their proposed mechanisms.

Язык: Английский

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DOXORUBICIN-RELATED CARDIOTOXICITY: REVIEW OF FUNDAMENTAL PATHWAYS OF CARDIOVASCULAR SYSTEM INJURY

Cardiovascular Pathology, Год журнала: 2024, Номер 73, С. 107683 - 107683

Опубликована: Авг. 6, 2024

Язык: Английский

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Cardiovascular therapeutic targets of sodium-glucose co-transporter 2 (SGLT2) inhibitors beyond heart failure

Pharmacology & Therapeutics, Год журнала: 2025, Номер 270, С. 108861 - 108861

Опубликована: Апрель 15, 2025

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are oral antidiabetic agents that have shown significant improvements in cardiovascular and renal outcomes among patients with heart failure (HF), regardless of diabetic status, establishing them as a cornerstone therapy. In addition to glycemic control the osmotic diuretic effect, inhibition SGLT2 improves endothelial function vasodilation, optimizing myocardial energy metabolism preserving cardiac contractility. Moreover, may exhibit anti-inflammatory properties attenuate acute ischemia/reperfusion injury, thereby reducing infarct size, enhancing left ventricular function, mitigating arrhythmias. These pleiotropic effects demonstrated efficacy across various conditions, ranging from chronic coronary syndromes extending arrhythmias, valvular disease, cardiomyopathies, cardio-oncology, cerebrovascular disease. This review provides an overview current literature on potential mechanisms underlying effectiveness wide range diseases beyond HF.

Язык: Английский

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Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Июнь 13, 2023

Type II diabetes mellitus (T2DM) is a metabolic disorder that poses serious health concern worldwide due to its rising prevalence. Hypertension (HT) frequent comorbidity of T2DM, with the co-occurrence both conditions increasing risk diabetes-associated complications. Inflammation and oxidative stress (OS) have been identified as leading factors in development progression T2DM HT. However, OS inflammation processes associated these two comorbidities are not fully understood. This study aimed explore changes levels plasma urinary inflammatory biomarkers, along mitochondrial biomarkers connected dysfunction (MitD). These markers may provide more comprehensive perspective disease from no diabetes, prediabetes, coexisting HT cohort patients attending clinic Australia. Three-hundred eighty-four participants were divided into four groups according status: 210 healthy controls, 55 prediabetic patients, 32 87 (T2DM+HT). Kruskal-Wallis χ2 tests conducted between detect significant differences for numerical categorical variables, respectively. For transition prediabetes interleukin-10 (IL-10), C-reactive protein (CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG), humanin (HN), p66Shc most discriminatory generally displaying elevated addition disrupted function revealed by HN. Disease T2DM+HT indicated lower through IL-10, interleukin-6 (IL-6), interleukin-1β (IL-1β), 8-OHdG oxidized glutathione (GSSG) levels, likely antihypertensive medication use +HT patient group. The results also better this group shown higher HN which can be attributed use. monocyte chemoattractant protein-1 (MCP-1) appeared independent medication, providing an effective biomarker even presence suggest review discriminating stages or absence Our further indicate usefulness use, especially respect known involvement progression, highlighting specific during therefore allowing targeted individualized treatment plan.

Язык: Английский

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Role of Oxidative Stress and Inflammation in Doxorubicin-Induced Cardiotoxicity: A Brief Account

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7477 - 7477

Опубликована: Июль 8, 2024

Cardiotoxicity is the main side effect of several chemotherapeutic drugs. Doxorubicin (Doxo) one most used anthracyclines in treatment many tumors, but development acute and chronic cardiotoxicity limits its clinical usefulness. Different studies focused only on effects long-term Doxo administration, recent data show that cardiomyocyte damage an early event induced by after a single administration can be followed progressive functional decline, leading to overt heart failure. The knowledge molecular mechanisms involved stage Doxo-induced paramount importance treating and/or preventing it. This review aims illustrate thought underlie cardiotoxicity, such as oxidative nitrosative stress, inflammation, mitochondrial dysfunction. Moreover, here we report from both vitro vivo indicating new therapeutic strategies prevent cardiotoxicity.

Язык: Английский

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A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms

Cardiovascular Drugs and Therapy, Год журнала: 2024, Номер unknown

Опубликована: Март 16, 2024

Abstract While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments have also come to the fore. These include cardiotoxicity, which can cause irreversible cardiac damages with long-term morbidity mortality. Despite continuous in-depth research on drugs, an improved knowledge underlying mechanisms cardiotoxicity are necessary for early detection management risk. Although most reviews focus cardiotoxic effect a specific individual chemotherapeutic agent, aim our review is provide comprehensive insight into various agents that induced their mechanisms. Characterization these underpinned by animal models clinical studies. In order gain complex mechanisms, we emphasize role inflammatory processes oxidative stress chemotherapy-induced changes. A better understanding identification interplay between chemotherapy inflammatory/oxidative hold some promise prevent or at least mitigate cardiotoxicity-associated mortality among cancer survivors.

Язык: Английский

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SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 116917 - 116917

Опубликована: Июнь 21, 2024

Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various signaling pathways exert protective effect on many human diseases. SIRT1 functioned important role occurrence progression sarcopenia through regulating key related protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance autophagy muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), SIRT1/live B1 (LKB1)/AMPK pathways. However, specific mechanisms these processes have not fully illuminated. Currently, several SIRT1-mediated interventions preliminarily developed, such activator polyphenolic compounds, exercising calorie restriction. In this review, we summarized predominant involved therapeutic modalities targeting for prevention prognosis sarcopenia.

Язык: Английский

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Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin

Journal of Controlled Release, Год журнала: 2024, Номер 369, С. 351 - 362

Опубликована: Апрель 3, 2024

Язык: Английский

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

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 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.

Язык: Английский

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