Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4753 - 4753

Published: April 26, 2024

Wilson disease is a genetic disorder of the liver characterized by excess accumulation copper, which found ubiquitously on earth and normally enters human body in small amounts via food chain. Many interesting details were published mechanistic steps, such as generation reactive oxygen species (ROS) cuproptosis causing copper dependent cell death. In patients with disease, also, increased iron deposits that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes subcellular organelles. All topics are covered this review article, addition diagnostic therapeutic issues disease. Excess Cu2+ primarily leads (ROS), evidenced early experimental studies exemplified detection hydroxyl radical formation using electron spin resonance (ESR) spin-trapping method. The ROS products follows principles Haber–Weiss reaction subsequent Fenton leading copper-related cuproptosis, thereby closely connected ROS. Copper due impaired biliary excretion caused inheritable malfunctioning or missing ATP7B protein. As result, disturbed cellular homeostasis prevails liver. Released from cells limited storage capacity, toxic circulation arrives at other organs, local injury. This explains why injures not only liver, but also brain, kidneys, eyes, heart, muscles, bones, explaining multifaceted clinical features Among these depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser–Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, arthralgia. addition, Coombs-negative hemolytic anemia key feature undetectable serum haptoglobin. modified Leipzig Scoring System helps diagnose Patients well-treated first-line chelators like D-penicillamine facilitate removal circulating bound albumin increase urinary excretion. Early chelation therapy improves prognosis. Liver transplantation an option viewed ultima ratio end-stage untreatable complications acute failure. finally thus be life-saving approach curative treatment replacing hepatic gene mutation. conclusion, representing molecular challenge.

Language: Английский

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Copper, Iron, Cadmium, and Arsenic, All Generated in the Universe: Elucidating Their Environmental Impact Risk on Human Health Including Clinical Liver Injury

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6662 - 6662

Published: June 17, 2024

Humans are continuously exposed to various heavy metals including copper, iron, cadmium, and arsenic, which were specifically selected for the current analysis because they among most frequently encountered environmental mankind industrial pollutants potentially causing human health hazards liver injury. So far, these issues poorly assessed remained a matter of debate, also due inconsistent results. The aim actual report is thoroughly analyze positive as well negative effects four on health. Copper iron correctly viewed pollutant elements essential maintaining part important enzymes metabolic pathways. Healthy individuals prepared through genetically based mechanisms maintain cellular copper homeostasis, thereby circumventing or reducing hazardous organ injury excessive amounts entering body. In few humans with gene aberration, however, may develop excessively accumulated can lead Wilson disease substantial deposition hemochromatosis. At molecular level, toxicities some traced back Haber Weiss Fenton reactions involving reactive oxygen species formed in course oxidative stress. On other hand, homeostasis cadmium arsenic cannot be provided, their life-long organs. Consequently, represent leading higher disability-adjusted life years increased mortality rates cancer non-cancer diseases. For unknown reasons, rarely observed. sum, good except those hemochromatosis at risk radical formation, while lack any beneficial but rather focus disability potential cancer. Primary efforts should emission metals.

Language: Английский

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The impact of biocorrosion and titanium ions release on peri-implantitis

Clinical Oral Investigations, Journal Year: 2025, Volume and Issue: 29(3)

Published: Feb. 25, 2025

Language: Английский

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The impact of toxic metal bioaccumulation on colorectal cancer: Unravelling the unexplored connection

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 906, P. 167667 - 167667

Published: Oct. 9, 2023

Colorectal cancer is a major public health concern, with increasing incidence and mortality rates worldwide. Environmental factors, including exposure to toxic metals, such as lead, chromium, cadmium, aluminium, copper, arsenic mercury, have been suggested play significant role in the development progression of this neoplasia. In particular, bioaccumulation metals can colorectal by regulating biological phenomenon associated both occurrence progression, cell death proliferation. Also, frequently these induce DNA mutations well-known oncogenes. This review provides critical analysis current evidence, highlighting need for further research fully grasp complex interplay between metal cancer. Understanding contribution essential targeted preventive strategies social interventions, ultimate goal reducing burden disease.

Language: Английский

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From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(5-6), P. 586 - 604

Published: Feb. 7, 2024

Language: Английский

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Construction of Al (III) ion selective electrode based on BN@SnP composite and its real-life applications

Chemical Papers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Language: Английский

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Rainwater quality in Special Economic Zone (SEZ) in Poland

Environmental Pollution, Journal Year: 2025, Volume and Issue: 370, P. 125866 - 125866

Published: Feb. 19, 2025

Language: Английский

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Cuproptosis: emerging biomarkers and potential therapeutics in cancers

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 7, 2023

The sustenance of human life activities depends on copper, which also serves as a crucial factor for vital enzymes. Under typical circumstances, active homeostatic mechanisms keep the intracellular copper ion concentration low. Excess ions cause excessive cellular respiration, causes cytotoxicity and cell death levels steadily rise above threshold. It is novel that mitochondrial ions, regulation. Cuproptosis now understood to play role in several pathogenic processes, including inflammation, oxidative stress, apoptosis. Copper type regulatory death(RCD).Numerous diseases are correlated with development homeostasis imbalances. One most popular areas study field cancer cuproptosis. has been discovered angiogenesis, proliferation, growth, metastasis all accumulation ions. concentrations can serve marker development. In order reference clinical research product, diagnosis, treatment cancer, this paper covers function imbalance malignant cancers related molecular pathways.

Language: Английский

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Mass spectrometry imaging of metals in tissues and cells: Methods and biological applications

Biochimica et Biophysica Acta (BBA) - General Subjects, Journal Year: 2023, Volume and Issue: 1868(2), P. 130329 - 130329

Published: Feb. 13, 2023

Language: Английский

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Implication of ferroptosis in hepatic toxicity upon single or combined exposure to polystyrene microplastics and cadmium

Environmental Pollution, Journal Year: 2023, Volume and Issue: 334, P. 122250 - 122250

Published: July 22, 2023

Language: Английский

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