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Endocrine, Metabolic & Immune Disorders... 2021Cell death is a fundamental biological phenomenon that contributes to the pathogenesis of various diseases. Regulation of iron and iron metabolism has received... (Review)
Review
BACKGROUND
Cell death is a fundamental biological phenomenon that contributes to the pathogenesis of various diseases. Regulation of iron and iron metabolism has received considerable research interests especially concerning the progression of metabolic diseases.
DISCUSSION
Emerging evidence shows that ferroptosis, a non-apoptotic programmed cell death induced by iron-dependent lipid peroxidation, contributes to the development of complex diseases such as non-alcoholic steatohepatitis, cardiomyopathy, renal ischemia-reperfusion, and neurodegenerative diseases. Therefore, inhibiting ferroptosis can improve the pathophysiology of associated metabolic diseases. This review describes the vital role of ferroptosis in mediating the development of certain metabolic diseases. Besides, the potential risk of iron and ferroptosis in atherosclerosis and cardiovascular diseases is also described. Iron overload and ferroptosis are potential secondary causes of death in metabolic diseases. Moreover, this review also provides potential novel approaches against ferroptosis based on recent research advances.
CONCLUSION
Several controversies exist concerning mechanisms underlying ferroptotic cell death in metabolic diseases, particularly in atherosclerosis. Since ferroptosis participates in the progression of metabolic diseases such as non-alcoholic steatohepatitis (NASH), there is a need to develop new drugs targeting ferroptosis to alleviate such diseases.
Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Cell Death; Ferroptosis; Humans; Iron; Macrophages; Metabolic Diseases; Non-alcoholic Fatty Liver Disease
PubMed: 32735532
DOI: 10.2174/1871530320666200731175328 -
Human & Experimental Toxicology Oct 2021Doxorubicin (DOX) is an anthracycline antibiotic. Despite its unwanted side effects, it has been successfully used in tumor therapy. Given that oxidative stress and...
Doxorubicin (DOX) is an anthracycline antibiotic. Despite its unwanted side effects, it has been successfully used in tumor therapy. Given that oxidative stress and inflammatory factors are essential to cardiotoxicity caused by DOX, we assumed that alamandine, which enhances endogenous antioxidants and has anti-inflammatory effects, may prevent DOX-induced cardiotoxicity. Rats received DOX (3.75 mg/kg) i.p on days 14, 21, 28, and 35 (total cumulative dose = 15 mg/kg) and alamandine (50 μg/kg/day) via mini-osmotic pumps for 42 days. At the end of the 42-day period, we evaluated hemodynamic parameters, electrocardiogram, cardiac troponin I (cTnI), superoxidase dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), inflammatory cytokines (tumor necrosis factor-α (TNF-α), IL-1β, NF-κB), apoptosis markers (caspase 3), and histopathology of haemotoxylin- and eosin-stained cardiac muscle fibers were evaluated. DOX significantly increased QT, corrected QT (QTc), and RR intervals. Alamandine co-therapy prevented ECG changes. Alamandine administration restored DOX-induced disruptions in the cardiac muscle architecture and vascular congestion. Alamandine co-therapy also alleviated other effects of DOX, including cardiac contractility, decreased systolic and diastolic blood pressure, and increased left ventricular end-diastolic pressure. Moreover, alamandine co-therapy substantially decreased the elevation of oxidative stress markers, inflammatory cytokines, and caspase 3 in DOX-treated rats. The results suggest that alamandine reduced DOX-induced cardiotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic activities.
Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Biomarkers; Cytokines; Doxorubicin; Gene Expression Regulation; Heart Diseases; Inflammation; Male; Oligopeptides; Random Allocation; Rats; Rats, Sprague-Dawley
PubMed: 33882726
DOI: 10.1177/09603271211010896 -
Oxidative Medicine and Cellular... 2022
Topics: Anthracyclines; Antibiotics, Antineoplastic; Autophagy; Cardiotoxicity; Humans; Inflammation; Neoplasms; Oxidative Stress
PubMed: 35464757
DOI: 10.1155/2022/9862524 -
Redox Biology Jan 2020Doxorubicin (DOX), or Adriamycin, an anthracycline antibiotic discovered serendipitously as a chemotherapeutic drug several decades ago, is still one of the most... (Review)
Review
Doxorubicin (DOX), or Adriamycin, an anthracycline antibiotic discovered serendipitously as a chemotherapeutic drug several decades ago, is still one of the most effective drugs for treating various adult and pediatric cancers (breast cancer, Hodgkin's disease, lymphoblastic leukemia). However, one of the major side effects of the continuous use of DOX is dose-dependent, long-term, and potentially lethal cardiovascular toxicity (congestive heart failure and cardiomyopathy) in cancer survivors many years after cessation of chemotherapy. In addition, predisposition to cardiotoxicity varied considerably among individuals. The long-held notion that DOX cardiotoxicity is caused by reactive oxygen species formed from the redox-cycling of DOX semiquinone lacks rigorous proof in a chronic animal model, and administration of reactive oxygen species detoxifying agents failed to reverse DOX-induced cardiac problems. In this review, I discuss the pros and cons of the reactive oxygen species pathway as a primary or secondary mechanism of DOX cardiotoxicity, the role of topoisomerases, and the potential use of mitochondrial-biogenesis-enhancing compounds in reversing DOX-induced cardiomyopathy. New approaches for well-designed clinical trials that repurpose FDA-approved drugs and naturally occurring polyphenolic compounds prophylactically to prevent or mitigate cardiovascular complications in both pediatric and adult cancer survivors are needed. Essentially, the focus should be on enhancing mitochondrial biogenesis to prevent or mitigate DOX-induced cardiotoxicity.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Child; Doxorubicin; Humans; Reactive Oxygen Species; Topoisomerase II Inhibitors
PubMed: 31790851
DOI: 10.1016/j.redox.2019.101394 -
Kardiologia Polska 2023
Topics: Humans; Pilot Projects; Anthracyclines; Microcirculation; Antibiotics, Antineoplastic
PubMed: 37190918
DOI: 10.33963/KP.a2023.0108 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2021Substances available in nature with potential therapeutic effects are the subject of research that raises tremendous hopes for new challenges in medicine. Fungi are the... (Review)
Review
Substances available in nature with potential therapeutic effects are the subject of research that raises tremendous hopes for new challenges in medicine. Fungi are the most common organisms in the ecosystem and the most interesting in this respect. This review discusses two species of edible fungi, used for centuries in Eastern natural medicine, with the best-documented effect - Hericium erinaceus (He) and Trametes versicolor (Tv). The results of in vivo and in vitro studies conducted on mice and human cell lines demonstrate immunomodulatory, potentially, anticancer, anti-inflammatory and neuroregenerative effects of substances isolated from these fungi. The substances contained in the extracts of He and Tv seem to have immunomodulatory effects that may support chemotherapy. The use of these extracts is justified stronger than the other supportive treat ments based on supplements.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibiotics, Antineoplastic; Cell Line, Tumor; Hericium; Humans; Immunologic Factors; Mice; Neurodegenerative Diseases; Polyporaceae
PubMed: 32697746
DOI: 10.2478/acph-2021-0007 -
European Journal of Medicinal Chemistry Jan 2021Marine natural products are known for their diverse chemical structures and extensive bioactivities. Renieramycins, the member of tetrahydroisoquinoline family of marine... (Review)
Review
Marine natural products are known for their diverse chemical structures and extensive bioactivities. Renieramycins, the member of tetrahydroisoquinoline family of marine natural products, arouse interests because of their strong antitumor activities and similar structures to the first marine antitumor agent ecteinascidin-743, approved by the European Union. According to the literatures, researches on the pharmacological activities of renieramycins mainly focus on their antitumor activities. In addition, by structural modification, derivatives of renieramycins show stronger antiproliferative activity and less accidental necrosis activity on cells. Nevertheless, the difficulties in extraction and separation hinder their further development. Hence, the synthetic chemistry work of renieramycins plays a key role in their further development. In this review, currently reported researches on the synthetic chemistry, pharmacological activities and structural modification of renieramycins are summarized, which will benefit future drug development and innovation.
Topics: Alkaloids; Anti-Infective Agents; Antibiotics, Antineoplastic; Antiprotozoal Agents; Biological Products; Molecular Structure; Neoplasms; Tetrahydroisoquinolines
PubMed: 33333398
DOI: 10.1016/j.ejmech.2020.113092 -
Journal of Natural Products May 2020Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (, and ), eight new 14-membered RALs (-), and one new 12-membered RAL (), along with...
Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (, and ), eight new 14-membered RALs (-), and one new 12-membered RAL (), along with five known 14-membered RALs (-), were identified from the fermentation of the soil-derived fungus sp. sb65. Their structures were established by detailed analyses of 1D and 2D NMR, HRESIMS, and X-ray diffraction crystallography. All new compounds were evaluated for their cytotoxic effects against three human cancer cell lines, along with their potential as TRAIL sensitizers in TRAIL-resistant A549 human lung adenocarcinoma cells and their immunosuppressive effects against ConA-induced T-cell and LPS-induced B-cell proliferation.
Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Crystallography, X-Ray; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Fermentation; HeLa Cells; Humans; Hypocreales; Immunosuppressive Agents; Lactones; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Mice, Inbred BALB C; Molecular Structure; Resorcinols
PubMed: 32323537
DOI: 10.1021/acs.jnatprod.9b01167 -
Soft Matter Oct 2019In this work, we synthesized electroactive and degradable microgels based on biomacromolecular building blocks, which enable the controlled release of therapeutic drugs....
In this work, we synthesized electroactive and degradable microgels based on biomacromolecular building blocks, which enable the controlled release of therapeutic drugs. Functional chitosan-poly(hydroquinone) (Ch:PHQ) microgels exhibiting redox-active and pH-sensitive properties were synthesized by an oxidative polymerization in an inverse miniemulsion system. Physically crosslinked microgels were formed by polymerization of hydroquinone in the presence of chitosan through the formation of hydrogen bonds between PHQ and Ch. A series of microgel samples with variable Ch : PHQ ratios were synthesized. These obtained microgels exhibit pH-responsive properties due to the protonation/deprotonation of amino-groups of chitosan in the microgel system. Poly(hydroquinone) is a redox-active polymer exhibiting a two-electron/proton-transfer behavior and conveys this property to the microgels as confirmed by cyclic voltammetry. In addition, the microgels can be switched by electrochemical means: they swell in the oxidized state or shrink in the reduced state. In the presence of urea or lysozyme, the microgels undergo a fast degradation due to the disruption of hydrogen bonds acting as physical crosslinks in the microgel networks or due to the cleavage of glucosidic linkages of the incorporated chitosan scaffold, respectively. Doxorubicin (DOX), an anticancer drug, could be effectively encapsulated into the microgels and released in the presence of an enzyme, indicating that these biodegradable microgels could be used as drug delivery vehicles for tumor cells.
Topics: Animals; Antibiotics, Antineoplastic; Chitosan; Doxorubicin; Drug Carriers; Electrochemical Techniques; Fibroblasts; Hydrogen Bonding; Hydroquinones; Mice; Microgels; Muramidase; Polymers; Urea
PubMed: 31642835
DOI: 10.1039/c9sm01390c -
Clinical Science (London, England :... Jun 2021Significant improvements in cancer survival have brought to light unintended long-term adverse cardiovascular effects associated with cancer treatment. Although capable... (Review)
Review
Significant improvements in cancer survival have brought to light unintended long-term adverse cardiovascular effects associated with cancer treatment. Although capable of manifesting a broad range of cardiovascular complications, cancer therapy-related cardiac dysfunction (CTRCD) remains particularly common among the mainstay anthracycline-based and human epidermal growth factor receptor-targeted therapies. Unfortunately, the early asymptomatic stages of CTRCD are difficult to detect by cardiac imaging alone, and the initiating mechanisms remain incompletely understood. More recently, circulating inflammatory markers, cardiac biomarkers, microRNAs, and extracellular vesicles (EVs) have been considered as early markers of cardiovascular injury. Concomitantly, the role of the endothelium in regulating cardiac function in the context of CTRCD is starting to be understood. In this review, we highlight the impact of breast cancer therapies on the cardiovascular system with a focus on the endothelium, and examine the status of circulating biomarkers, including inflammatory markers, cardiac biomarkers, microRNAs, and endothelial cell-derived EVs. Investigation of these emerging biomarkers may uncover mechanisms of injury, detect early stages of cardiovascular damage, and elucidate novel therapeutic approaches.
Topics: Antibiotics, Antineoplastic; Cardiovascular Diseases; Cardiovascular System; Heart; Heart Diseases; Humans; Neoplasms
PubMed: 34136902
DOI: 10.1042/CS20210059