Redox Biology, Год журнала: 2025, Номер 83, С. 103654 - 103654
Опубликована: Апрель 30, 2025
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6662 - 6662
Опубликована: Июнь 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.
Язык: Английский
Процитировано
23
Materials Today Bio, Год журнала: 2024, Номер 27, С. 101143 - 101143
Опубликована: Июль 2, 2024
Recent FDA modernization act 2.0 has led to increasing industrial R&D investment in advanced
Язык: Английский
Процитировано
11
Annals of Hepatology, Год журнала: 2015, Номер 14(1), С. 7 - 19
Опубликована: Янв. 1, 2015
Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, neglect of rare adverse reactions including liver injury. To compile worldwide cases injury by TCM, we undertook a selective literature search in the PubMed database and searched for items Medicine, Asian Oriental also combined terms hepatotoxicity or herb induced The focused primarily English-language case reports, series, clinical reviews. We identified reported 77 relevant publications 57 different herbs mixtures which were further analyzed causality Council International Organizations Medical Sciences (CIOMS) scale, positive reexposure test results, both. Causality established 28/57 mixtures, Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Xue Jin Bu Huan, Jue Ming Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao. In conclusion, this compilation establishes TCM aiding diagnosis physicians who care patients disease possibly related to TCM.
Язык: Английский
Процитировано
80
Hepatology Communications, Год журнала: 2024, Номер 8(4)
Опубликована: Апрель 1, 2024
Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, cholestatic disease (bland hepatitis), failure, severe features portal hypertension, decompensation known unknown cirrhosis that can lead to acute-on-chronic failure. Acute necrosis, hepatocellular canalicular cholestasis, herb-induced CAM-triggered autoimmune hepatitis, granulomatous steatohepatitis, vanishing bile duct syndrome are common biopsy findings in CAM-DILI. presence preexisting predicts injury, risk progression decreased transplant-free survival patients This review discusses global epidemiology trends CAM-DILI, presentation, assessment outcomes, commonly emerging threats context hepatotoxic herbs, pragmatic “liver beneficial” herbs health care myths, patient communication, regulatory framework, future directions research CAM.
Язык: Английский
Процитировано
8
PLoS ONE, Год журнала: 2025, Номер 20(2), С. e0317680 - e0317680
Опубликована: Фев. 6, 2025
Background Drug-induced autoimmune-like hepatitis (DI-ALH) is a potentially life-threatening condition that can lead to acute liver failure and necessitate transplantation. While the association between certain drugs DI-ALH has been documented, comprehensive analysis of drug-related signals in large, real-world pharmacovigilance database lacking. This study aimed systematically identify linked by analyzing adverse event reports from U.S. Food Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) database. Methods We searched FAERS for term "autoimmune hepatitis" extracted first quarter 2004 2024. Positive signal were identified using Proportional Ratio (PRR), Odds (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), Empirical Geometric Mean (EBGM). To confirm significant drug-adverse association, each method had meet predefined thresholds: PRR ROR, values considered if lower 95% confidence interval (CI) was greater than 1 at least three identified; BCPNN, an Information Component (IC025) 0 indicated signal; EBGM, value 2 (EBGM05) used denote positive signal. Results A total 5,723 Disproportionality 50 with strong associations DI-ALH, biologics, statins, antibiotics, antiviral representing most common categories. Among these, nitrofurantoin (ROR 94.79, CI 78.53–114.41), minocycline 77.82, 65.09–93.05), nivolumab 47.12, 15.06–147.39) exhibited strongest signals. Additionally, several previously unreported drugs, including mesalazine, aldesleukin, onasemnogene abeparvovec-xioi, nefazodone, as having DI-ALH. These findings consistent across all four detection methods, further validating robustness associations. Conclusion provides assessment associated through rigorous multiple methods. By identifying both well-known underreported this contributes more complete understanding drug-induced injury. The have important implications strategies clinical risk assessment. However, limitations inherent database, such underreporting potential reporting bias, should be considered. Further validation warranted these
Язык: Английский
Процитировано
1
Annals of Surgical Oncology, Год журнала: 2025, Номер unknown
Опубликована: Март 11, 2025
Язык: Английский
Процитировано
1
Future Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 11(1)
Опубликована: Март 28, 2025
Abstract Background Drug-induced liver injury (DILI) is a significant adverse drug reaction, manifesting through range of clinical presentations from mild enzyme to acute failure. Main text This review provides comprehensive overview DILI, emphasizing the differences between intrinsic and idiosyncratic DILI. The underlying molecular mechanisms, like mitochondrial dysfunction, oxidative stress, immune-mediated responses, are discussed in detail. epidemiology DILI explored various retrospective prospective studies, highlighting role specific medications individual susceptibility factors. also addresses challenges diagnosing impact on development practice. Conclusion poses threat due its potential for causing failure associated mortality. To improve patient outcomes, further research crucial identify effective therapeutic interventions.
Язык: Английский
Процитировано
1
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Апрель 10, 2024
Idiosyncratic drug-induced liver injury (iDILI) is a major concern in drug development because its occurrence unpredictable. Presently, iDILI prediction challenge, and cell toxicity observed only at concentrations that are much higher than the therapeutic doses preclinical models. Applying proprietary educating technology, we developed person-dependent spheroid system contains autologous educated immune cells can detect risk concentrations. Integrating this into high-throughput screening platform will help pharmaceutical companies accurately of new molecules de-risking development.
Язык: Английский
Процитировано
4
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Июнь 27, 2024
Background Acetaminophen (APAP) is commonly used as an antipyretic analgesic. However, acetaminophen overdose may contribute to liver injury and even failure. Acetaminophen-induced (AILI) closely related mitochondrial oxidative stress dysfunction, which play critical roles in cuproptosis. Here, we explored the potential role of cuproptosis-related genes (CRGs) AILI. Methods The gene expression profiles were obtained from Gene Expression Omnibus database. differential CRGs was determined between AILI control samples. Protein protein interaction, correlation, functional enrichment analyses performed. Machine learning identify hub genes. Immune infiltration evaluated. mouse model established by intraperitoneal injection APAP solution. Quantitative real-time PCR western blotting validate model. copper content samples AML12 cells quantified using a colorimetric assay kit. Ammonium tetrathiomolybdate (ATTM), administered models order investigate effects chelator on Results analysis identified 7,809 differentially expressed genes, 4,245 downregulated 3,564 upregulated. Four optimal feature (OFGs; SDHB, PDHA1, NDUFB2, NDUFB6) through intersection two machine algorithms. Further nomogram, decision curve, calibration curve confirmed diagnostic predictive efficacy four OFGs. Enrichment indicated that OFGs involved multiple pathways, such IL-17 pathway chemokine signaling pathway, are progression. revealed macrophages more abundant than samples, whereas eosinophils endothelial less abundant. Subsequently, successfully established, histopathological hematoxylin–eosin staining along with function tests significant induction group. Consistent expectations, both mRNA levels exhibited substantial decrease. administration ATTAM effectively mitigates elevation induced cells. systemic ATTM did not significantly alleviate Conclusion This study first pathological process offered novel insights into its underlying pathogenesis.
Язык: Английский
Процитировано
4
Drug Metabolism Reviews, Год журнала: 2024, Номер 56(2), С. 97 - 126
Опубликована: Фев. 5, 2024
Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of 34 antidepressants discussed in this review, four have been withdrawn from market due to hepatotoxicity, and others carry boxed warnings idiosyncratic toxicity. The clinical economic implications antidepressant-induced injury substantial, but underlying mechanisms remain elusive. Drug-induced may involve host immune system, parent drug, or its metabolites, reactive drug metabolites one most commonly referenced risk factors. Although precise mechanism by which toxicity is induced be difficult determine, identifying cause can offer valuable insights decreasing bioactivation potential candidates during discovery process. A comprehensive understanding metabolic pathways mitigate adverse drug-drug interactions caused elevated formation metabolites. This review provides a overview current state knowledge on antidepressant bioactivation, metabolizing enzymes responsible their implication hepatotoxicity. information resource medicinal chemists, toxicologists, clinicians engaged fields development, toxicity, treatment.
Язык: Английский
Процитировано
3