The role of Juniperus Macrocarpa extract as anti-inflammatory and antioxidant on methotrexate-induced acute liver injury in rat model

F1000Research, Journal Year: 2025, Volume and Issue: 14, P. 131 - 131

Published: Jan. 27, 2025

Methotrexate (MTX) is an antifolate medication indicated to treat array of tumors and autoinflammatory maladies. MTX may exhibit harmful impacts on multiple organs, especially liver injury cirrhosis. Juniperus macrocarpa a medicinal herb enriched with polyphenols flavonoids featuring robust anti-inflammatory antioxidative benefits. To evaluate the hepatoprotective effects aqueous extract MTX-aggravated toxicity. The study involved 20 male middle-aged albino rats, arbitrarily allocated into 4 groups 5 animals each. Group 1 (control) were given distilled water (DW) once daily for two weeks. 2 got intraperitoneal single dose (20 mg/kg) Rats in 3 dosages 100 mg 200 extract, respectively, weeks before receiving injection. extracts at both low high doses substantially alleviated MTX-provoked biochemical alterations, as evidenced by decreased levels inflammatory parameters including TNF-α IL-6 hepatic enzymes ALT, AST, ALP. also significantly boosted anti-oxidant like SOD GPX. Moreover, attenuated congestive degenerative changes, improved histopathological findings. anti-oxidative activities are promising approach ameliorating hepatotoxicity.

Language: Английский

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Paeoniflorin Attenuates APAP-Induced Liver Injury via Intervening the Crosstalk Between Hepatocyte Pyroptosis and NETs

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1493 - 1493

Published: Feb. 11, 2025

(1) Liver injury caused by an overdose of acetaminophen (APAP) represents a major public health concern. Paeoniflorin (PF) has been reported to have anti-inflammatory and liver-protective effects, but the underlying mechanisms remain unclear. This study aimed investigate effect PF on crosstalk between pyroptosis NETs in AILI. (2) APAP-treated C57BL/6J mice were used demonstrate protective liver injury. HepG2 dHL-60 cells cultured effects hepatocyte neutrophil extracellular traps (NETs) vitro. Moreover, cell co-culture experiments performed, treated with NETs-depleting agent inhibitor improvement AILI induced through regulating NETs. (3) significantly alleviated Additionally, inhibited expression pyroptosis-related proteins, high-mobility group box 1 (HMGB1), NETs-associated proteins vitro vivo. The demonstrated that not only triggered pyroptosis, also suppressed In depleted neutrophils, level notably decreased, indicating diminished impact PF. Similarly, formation was reduced receiving compared APAP group. Compared DNase I alone, reduction combined serum ALT AST levels decreased from 46.857% 39.927% 44.347% 33.419%, respectively. DSF 45.347% 36.419%, (4) therapeutic Its mechanism involves regulation research substantiates pharmacological promise as intervention for acute

Language: Английский

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Immunology Highlights of Four Major Idiosyncratic DILI Subtypes Verified by the RUCAM: A New Evidence-Based Classification

Livers, Journal Year: 2025, Volume and Issue: 5(1), P. 8 - 8

Published: Feb. 14, 2025

Conventionally, drug-induced liver injury (DILI) exists in two types: idiosyncratic and intrinsic. Both types are classified as non-immune disorders, thereby ignoring that some iDILI cases may have an immune or autoimmune background requires a different therapeutic approach because steroids be helpful. The purpose of this analysis was to analyze classify the subtypes which, indeed, show features among four cohorts, namely DILI type 1: hepatitis (DIAIH), differentiated from classic drug-unrelated (AIH); 2: human leucocyte antigen-based hepatitis; 3: anti-cytochrome P450-based 4: immune-based associated with Stevens–Johnson syndrome (SJS) toxic epidermal necrolysis (TEN). In conclusion, traditional non-autoimmune iDILI, well subtypes, now clinically characterized by broadly applied Roussel Uclaf Causality Assessment Method (RUCAM), facilitating additional immunology therapy studies for all which could benefit steroid treatment.

Language: Английский

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Drug-Induced Liver Injury—Pharmacological Spectrum Among Children

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2006 - 2006

Published: Feb. 25, 2025

Drug-induced liver injury (DILI) is one of the main causes acute failure in children. Its incidence probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and list expanding. The aim this review to describe DILI pathogenesis emphasize accountable for child order aid its recognition. Intrinsic well described terms mechanism, incriminated drugs, toxic dose. Conversely, idiosyncratic (iDILI) unpredictable, occurring a result particular response drug administration, occurrence cannot be foreseen clinical studies. Half pediatric iDILI cases linked antibiotics, mostly amoxicillin-clavulanate, immune-allergic group, while autoimmune hallmark minocycline nitrofurantoin. Secondly, antiepileptics responsible 20% cases, children being more prone caused by these agents than adults. A similar tendency was observed anti-tuberculosis higher incidences reported below three years old. Current data show growing related antineoplastic agents, atomoxetine, albendazole, so that it advisable clinicians maintain high index suspicion regarding iDILI.

Language: Английский

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Insights into Medication-induced Liver Injury: Understanding and Management Strategies

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 101976 - 101976

Published: March 1, 2025

Drug-induced liver injury (DILI) has increasingly become a major concern in Western countries since the late 1960s, with an estimated annual incidence of 13.9-19.1 cases per 100,000 people. DILI is significant cause acute failure, exhibiting high mortality rate 10-50 %. Its etiology includes medications, herbal products, and dietary supplements, exacerbated by pre-existing conditions, sonorities, pregnancy, nutritional deficiencies. It categorized into intrinsic idiosyncratic reactions. Intrinsic DILI, dose-dependent predictable, primarily caused substances like paracetamol, which leads to toxicity through direct metabolic pathways. In contrast, less common, unpredictable, affects susceptible individuals, non-steroidal anti-inflammatory drugs, antibiotics, cardiovascular agents frequently implicated hospitals. Oxidative stress, mitochondrial dysfunction, bile salt export inhibition, stress on endoplasmic reticulum are some DILI-related pathophysiology. Diagnosis relies biochemical tests, serological markers, radiological investigations, biopsy. Management strategies emphasize identification cessation offending supportive care, specific treatment options targeted culprit drugs. depends severity nature injury.

Language: Английский

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Potential of connexin 32 as a predictive marker for drug-induced cholestatic liver injury in a collagen vitrigel-culture model of HepG2-NIAS cells, a new subline of HepG2 cells, with bile canaliculus-like structures

The Journal of Toxicological Sciences, Journal Year: 2025, Volume and Issue: 50(3), P. 135 - 145

Published: Jan. 1, 2025

Cholestatic drug-induced liver injury (DILI) is caused by the aberrant excretion of bile acids (BAs) from hepatocytes via canaliculus-like structures (BCLSs) into ducts. The precise in vitro evaluation method for cholestatic DILI has not been established due to a lack specific markers and cell resources. We previously reported that HepG2-NIAS cells cultured on collagen vitrigel (CV) membrane formed BCLSs with high protein expression transporters involved BAs, including salt export pump (BSEP). In this study, potential connexin (Cx) 32, component gap junction, as predictive marker was investigated using CV-culture model cells. were treated 7 drugs different DILI-risk levels, toxicity Cx32 evaluated. Cell significantly increased only (troglitazone cyclosporine A) but also chlorpromazine low DILI-risk. Furthermore, troglitazone enhanced co-treatment taurocholate, suggesting involvement inhibition BA BSEP DILI. contrast, total co-localization F-actin, which composed BCLSs, drugs. Treatment induced zonula occludens (ZO)-1, supports concerted Cx32. These results suggest may be prominent

Language: Английский

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A Theranostic Three-photon Fluorescent Mn Complex with Mixed Double and Triple Bond for Drug-Induced Liver Injury: ONOO- Activatable and CO-Releasing

Talanta, Journal Year: 2025, Volume and Issue: unknown, P. 127956 - 127956

Published: March 1, 2025

Language: Английский

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Immunogenic adverse events to CFTR modulators – An international survey

Journal of Cystic Fibrosis, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Blood toxicogenomics reveals potential biomarkers for management of idiosyncratic drug-induced liver injury

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: March 25, 2025

Introduction: Accurate diagnosis, assessment, and prognosis of idiosyncratic drug-induced liver injury (IDILI) is problematic, in part due to the shortcomings traditional blood biomarkers. Studies rodents healthy volunteers have supported that RNA transcript changes whole may address some these shortcomings. Methods: In this study, we conducted RNA-Seq analysis on peripheral samples collected from 55 patients with acute IDILI 17 injuries not attributed IDILI. Results discussion: Three differentially expressed genes (DEGs; CFD , SQLE INKA1 ) were identified as significantly associated vs. other injuries. No DEGs comparing 5 autoimmune hepatitis, suggesting possible common underlying mechanisms. Two ( VMO1 EFNA1 hepatocellular compared mixed/cholestatic injury. When severe milder compared, over 500 DEGs. The top pathways had down regulation multiple T-cell specific genes. Further analyses confirmed could largely be accounted for by a fall concentration circulating T-cells during DILI, perhaps exhaustion or sequestration cells liver. Exploration individual causal agents was unsuccessful, but isoniazid-induced demonstrated 25 non-isoniazid cases. Finally, among 14 jaundice (i.e., Hy’s Law cases), 39 between 4 fatal transplantation outcomes those recovered. These findings suggest potential blood-based transcriptomic biomarkers aid diagnosis prognostic stratification

Language: Английский

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Identification of key immune genes of drug-induced liver injury induced by tolvaptan based on bioinformatics

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

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