Unraveling DINCH – Induced hepatotoxicity mechanisms via network toxicology and molecular docking with experimental validation DOI

Jingxin Xin,

Chengbin Zhou,

Ying Wang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 299, P. 118305 - 118305

Published: May 19, 2025

Language: Английский

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

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

Citations

21

Liver-on-chips for drug discovery and development DOI Creative Commons
Viraj Mehta,

Guruswamy Karnam,

Vamsi Madgula

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 27, P. 101143 - 101143

Published: July 2, 2024

Recent FDA modernization act 2.0 has led to increasing industrial R&D investment in advanced

Language: Английский

Citations

10

Drug-induced autoimmune-like hepatitis: A disproportionality analysis based on the FAERS database DOI Creative Commons

Wangyu Ye,

Yuan Ding, Meng Li

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0317680 - e0317680

Published: Feb. 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

Language: Английский

Citations

1

Serum Enzymes and Pathologic Complete Response to the Addition of Targeted Therapy in Neoadjuvant Chemotherapy for HER2-Positive Breast Cancer Patients DOI

Zongshun Chen,

Jing Zhang, Wei Chen

et al.

Annals of Surgical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

Citations

1

Exploring drug-induced liver injury: comprehensive insights into mechanisms and management of hepatotoxic agents DOI Creative Commons
Asmaa Saleh,

Thanaa A. El‐Masry,

Aya H. El-Kadem

et al.

Future Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 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.

Language: Английский

Citations

1

Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases DOI Creative Commons
Rolf Teschke, Li Zhang,

Hong-Zhu Long

et al.

Annals of Hepatology, Journal Year: 2015, Volume and Issue: 14(1), P. 7 - 19

Published: Jan. 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.

Language: Английский

Citations

80

Complementary and alternative medicines and liver disease DOI Creative Commons
Cyriac Abby Philips, Arif Hussain Theruvath, R. D. Ravindran

et al.

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(4)

Published: April 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.

Language: Английский

Citations

6

Exploiting the predictive power of educated spheroids to detect immune-mediated idiosyncratic drug-induced liver injury: the case of troglitazone DOI Creative Commons

Salomé Roux,

Sara Cherradi, Hong Tuan Duong

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 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.

Language: Английский

Citations

4

Identification and validation of cuproptosis-related genes in acetaminophen-induced liver injury using bioinformatics analysis and machine learning DOI Creative Commons

Zhenya Guo,

Jiaping Liu,

Guozhi Liang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 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.

Language: Английский

Citations

4

N-acetylcysteine use in a cocaine-induced liver failure: a case report DOI Creative Commons

Vanessa Biering,

Ronan Bellouard,

Maëlle Martin

et al.

Frontiers in Toxicology, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 15, 2025

Cocaine intoxication and abuse is a worldwide problem that can be the cause of numerous acute medical complications, including severe hepatitis. Although these cases are scarce, they extremely serious may lead to liver transplantation or death. Management toxic hepatitis, once causative agent has been discontinued, essentially symptomatic, based on clinical biological monitoring prevention complications related We present case 28-year-old woman admitted emergency department for hepatitis due cocaine intoxication. In addition sharp rise in her enzymes, patient also presented metabolic acidosis, renal failure, rhabdomyolysis. Treatment consisted administering N-acetylcysteine (NAC), dialysis, additional supportive measures. An improvement function with decrease transaminases occurred after NAC administration. The toxicokinetics major metabolites chemistry concentrations were monitored. usual management measures administration should investigated further, although it currently used only acetaminophen

Language: Английский

Citations

0