Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2668 - 2668

Published: Feb. 25, 2024

Hemochromatosis represents clinically one of the most important genetic storage diseases liver caused by iron overload, which is to be differentiated from hepatic overload due excessive release erythrocytes in patients with hemolytic disorders. This disorder under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), gut microbiome, and alcohol abuse as a risk factor, are all topics this review article. Triggered released intracellular free ferritin via autophagic process ferritinophagy, ferroptosis involved hemochromatosis specific form iron-dependent regulated cell death. develops course mitochondrial injury associated additional accumulation, followed production ROS lipid peroxidation. A low fecal content during therapeutic depletion reduces colonic inflammation oxidative stress. In clinical terms, an essential trace element required for human health. Humans cannot synthesize must take it up iron-containing foods beverages. Under physiological conditions, healthy individuals allow homeostasis restricting extent intestinal depending on realistic demand, avoiding uptake excess. For condition, body has no chance adequately compensate through removal. hemochromatosis, molecular finetuning set off mutations high-FE2+ (HFE) genes that lead lack hepcidin or resistance part ferroportin binding. major mechanism increased stores body. Hepcidin liver-derived peptide, impairs enterocytes macrophages interacting ferroportin. As result, accumulates various organs including liver, severely injured causes hemochromatosis. diagnosis difficult establish uncharacteristic features. Among these asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, cardiopathy. Diagnosis initially suspected serum levels ferritin, non-specific parameter also elevated inflammatory excluded safer diagnostic side. facilitated if combined fasting transferrin saturation, testing, family screening. Various attempts were published algorithms. However, none based evidence quantitative results derived scored key features opposed other known complex diseases. autoimmune hepatitis (AIH) drug-induced (DILI). both diseases, algorithms used line artificial intelligence (AI) principles ascertain diagnosis. The first-line therapy involves regular life-long phlebotomy remove blood, improves prognosis may prevent development end-stage disease such cirrhosis hepatocellular carcinoma. Liver transplantation rarely performed, confined acute failure. conclusion, ROS, concomitant play contributing role requires early initiation treatment.

Language: Английский

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Triptolide induced spermatogenesis dysfunction via ferroptosis activation by promoting K63-linked GPX4 polyubiquitination in spermatocytes

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 399, P. 111130 - 111130

Published: July 2, 2024

Language: Английский

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Cuproptosis: Mechanisms, biological significance, and advances in disease treatment—A systematic review

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(9)

Published: Sept. 1, 2024

Copper is an essential trace element for biological systems, as it plays a critical role in the activity of various enzymes and metabolic processes. However, dysregulation copper homeostasis closely associated with onset progression numerous diseases. In recent years, copper-induced cell death, novel form cellular demise, has garnered significant attention. This process characterized by abnormal accumulation intracellular ions, leading to dysfunction eventual death. toxicity occurs through interaction acylated tricarboxylic acid (TCA) cycle. results subsequent protein aggregation, causing proteotoxic stress ultimately resulting Despite promise these findings, detailed mechanisms broader implications cuproptosis remain underexplored. Therefore, our study aimed investigate death autophagy, focusing on molecular cuproptosis. We also discuss advancements copper-related research across diseases tumors, providing insights future studies potential therapeutic applications.

Language: Английский

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Heavy metal contamination in fish: sources, mechanisms and consequences

Aquatic Sciences, Journal Year: 2024, Volume and Issue: 86(4)

Published: Sept. 19, 2024

Language: Английский

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Treatment of Drug-Induced Liver Injury

Biomedicines, Journal Year: 2022, Volume and Issue: 11(1), P. 15 - 15

Published: Dec. 21, 2022

Current pharmacotherapy options of drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use offending drug must be stopped as soon DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, taken overdose commonly lead intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) intravenous antidote treatment with N-acetylcysteine (NAC) patients N-acetyl-p-aminophenol (APAP) overdose. Good data recommending caused hundreds different lacking. Indeed, a recent analysis revealed that just eight RCTs have been published, only two out were cases for causality worldwide Roussel Uclaf Causality Assessment Method (RUCAM), representing overall significant methodology flaw, results lacking RUCAM misleading since many known attributable erroneously nondrug alternative causes. In line these major shortcomings mostly based on anecdotal reports, glucocorticoids (GCs) other immuno-suppressants given empirically carefully selected exhibiting autoimmune features or immune checkpoint inhibitors (ICIs), while some cholestatic benefit from ursodeoxycholic acid use; hepatic sinusoidal obstruction syndrome (HSOS) coagulopathy risks, indication anticoagulants should considered. view mechanistic factors such microsomal cytochrome P450 generation reactive oxygen species (ROS), ferroptosis toxicity intracellular iron, modification gut microbiome, additional therapy available future. summation, stopping still first most instances acute various therapies applied good awaiting further using updated asks strict exclusion inclusion details like criteria provides valid rankings probable highly grades.

Language: Английский

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The association between endocrine disrupting chemicals and MAFLD: Evidence from NHANES survey

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 256, P. 114836 - 114836

Published: March 29, 2023

Previous studies on the association of endocrine-disrupting chemicals (EDCs) with metabolic dysfunction-associated fatty liver disease (MAFLD) are very limited. This study analyzed EDCs exposure MAFLD among 5073 American adults from 2017-2018 National Health and Nutrition Examination Survey. The results showed that increased to 3 metabolites (namely As, DiNP PFOA) were significantly associated MAFLD, odds ratio which 1.819 (95% CI: 1.224, 2.702), 1.959 3.136) 2.148 1.036, 4.456), respectively. Further, bayesian kernel machine regression model also revealed phthalates was strongly connected particularly in females elderly over 65. Moderating effect analysis suggested higher body mass index (BMI) inflammatory diet habit (indicated by dietary index) strengthened between whereas population level insulin sensitivity lower risk. In conclusion, our suggest either single or combined is link MAFLD. Our findings encourage people sustain a healthy diet, normal levels BMI, may help alleviate risk EDCs. These us better understand provide effective evidences for preventing aspect.

Language: Английский

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Associations of five blood heavy metals with hepatitis B virus infection and immunity in adults: a cross-sectional study

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 23, 2024

Abstract Background Heavy metal pollution has emerged as a significant concern for human health, prompting increased awareness of its potential adverse effects. While previous research established connection between heavy metals and liver function biomarkers, the specific relationship HBV infection remains unexplored. This cross-sectional study aims to investigate correlations five blood - lead, cadmium, mercury, manganese, selenium presence HBsAg, HBsAb, HBcAb in adults. Methods The utilized data from NHANES 2007–2018. Participants were classified into four groups based on their infectious status, association was analyzed using multiple logistic regression stratification analysis. Results A total 8431 participants included, with 5 436 Susceptible, 1 765 Vaccinated, 865 Natural Infection, 103 Acute/Chronic Infection. Vaccinated group exhibited lower mean age (34.52 ± 14.16 years) compared other groups. Statistically differences concentrations (except selenium) observed among ( P < 0.001). After adjusting covariates, lead significantly associated (Q2: OR 2.37, 95%CI 1.04–5.39; Q3: 2.34, 1.01–5.40), positive trends high mercury (Q4: 3.03, 1.31–7.04) manganese 2.52, 1.20–5.28). Furtherly, reduced protection HBsAb 0.84, 0.73–0.97; 0.77, 0.66–0.90; Q4: 0.83, 0.70–0.98). Subgroup analysis indicated that cadmium an risk Asians (OR 1.36, 1.03–1.78) individuals BMI range 25 30 1.60, 1.17–2.18). Conclusions study’s findings suggest correlation elevated Pb immunization rates against hepatitis B. Individuals HBsAg exhibit Se higher Hg Mn concentrations.

Language: Английский

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Single is not combined: The role of Co and Ni bioavailability on toxicity mechanisms in liver and brain cells

Chemosphere, Journal Year: 2024, Volume and Issue: 357, P. 142091 - 142091

Published: April 20, 2024

The two trace elements cobalt (Co) and nickel (Ni) are widely distributed in the environment due to increasing industrial application, for example lithium-ion batteries. Both metals known cause detrimental health impacts humans when overexposed both supposed be a risk factor various diseases. individual toxicity of Co Ni has been partially investigated, however underlying mechanisms, as well interactions remain unknown. In this study, we focused on treatment liver carcinoma (HepG2) astrocytoma (CCF-STTG1) cells model target sites these metals. We investigated their effects single combined exposure cell survival, death bioavailability, induction oxidative stress. combination CoCl2 NiCl2 resulted higher levels with subsequent decreased amount compared treatment. Only led RONS increased GSSG formation, while apoptosis necrosis seem involved mechanisms NiCl2. Collectively, study demonstrates cell-type specific toxicity, HepG2 representing more sensitive line. Importantly, is toxic than exposure, which may originate partly from respective cellular content. Our data imply that major mechanism joint associated More studies needed assess after such advance an improved hazard prediction less artificial real-life scenarios.

Language: Английский

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A dual-response fluorescent probe to reveal the role of ferroptosis in drug-induced liver injury

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 495, P. 153592 - 153592

Published: June 28, 2024

Language: Английский

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Adsorptive Removal of Pb2+ from Aqueous Solution by Magnetic Biodegradable and Polymeric Cellulose/Nylon 6@Fe3O4 Nanocomposite Encapsulated with Chitosan

Desalination and Water Treatment, Journal Year: 2024, Volume and Issue: unknown, P. 100782 - 100782

Published: Sept. 1, 2024

Language: Английский

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