Background And Aim: Drug-induced liver injury occurs frequently and can be life threatening. Although drug-induced liver injury is mainly caused by the direct drug cytotoxicity, increasing evidence suggests that the interplay between hepatocytes and immune cells can define this pathogenic process. Here, we interrogate the role of the pattern recognition scavenger receptor A (SRA) for regulating hepatic inflammation and drug-induced liver injury.
Approach And Results: Using acetaminophen (APAP) or halothane-induced liver injury models, we showed that SRA loss renders mice highly susceptible to drug hepatotoxicity, indicated by the increased mortality and liver pathology. Mechanistic studies revealed that APAP-induced liver injury exaggerated in the absence of SRA was associated with the decreased anti-inflammatory and prosurvival cytokine IL-10 concomitant with excessive hepatic inflammation. The similar correlation between SRA and IL-10 expression was also seen in human following APAP uptake. Bone marrow reconstitution and liposomal clodronate depletion studies established that the hepatoprotective activity of SRA mostly resized in the immune sentinel KCs. Furthermore, SRA-facilitated IL-10 production by KCs in response to injured hepatocytes mitigated activation of the Jun N-terminal kinase-mediated signaling pathway in hepatocytes. In addition, supplemental use of IL-10 with N -acetylcysteine, only approved treatment of APAP overdose, conferred mice improved protection from APAP-induced liver injury.
Conclusion: We identify a novel hepatocyte-extrinsic pathway governed by the immune receptor SRA that maintains liver homeostasis upon drug insult. Giving that drug (ie, APAP) overdose is the leading cause of acute liver failure, targeting this hepatoprotective SRA-IL-10 axis may provide new opportunities to optimize the current management of drug-induced liver injury.
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http://dx.doi.org/10.1097/HEP.0000000000000044 | DOI Listing |
Talanta
January 2025
School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China. Electronic address:
As a serine hydrolase synthesized by the liver, butyrylcholinesterase (BChE) is an important biomarker in the clinical diagnosis of liver diseases. To track BChE activity in drug-induced liver injury, we designed a deep-red BChE-activatable fluorescent probe (CYL-BChE) with hemi-cyanine structure by using a cyclopropyl carbonyl group as a specific recognition moiety. Its near-infrared absorption wavelength (665 nm) and emission wavelength (762 nm) provide excellent tissue penetration capabilities, making it suitable for biological imaging.
View Article and Find Full Text PDFEXCLI J
November 2024
Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M1 5GD, UK.
Farnesol (FAR) is a sesquiterpene alcohol that exists in many fruits and vegetables and possesses promising anti-inflammatory and antioxidant activities. Cadmium (Cd) is an environmental pollutant known for its serious health effects. Liver injury associated with oxidative stress is a hazardous consequence of exposure to Cd.
View Article and Find Full Text PDFACG Case Rep J
January 2025
Stony Brook Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stony Brook University Hospital, Stony Brook, NY.
Although herpes simplex virus, Epstein-Barr virus, and hemophagocytic lymphohistiocytosis are known causes of severe acute liver injury with or without liver failure, these diseases occur almost exclusively in immunocompromised and elderly patients. We report a case of an immunocompetent young man with no medical history who presented with a subacute cough and persistent fevers in the setting of a penile chancre. He was found to have severely elevated liver chemistries and was subsequently diagnosed with hemophagocytic lymphohistiocytosis because of disseminated herpes simplex virus type 1 and Epstein-Barr virus coinfection.
View Article and Find Full Text PDFInfect Drug Resist
January 2025
Department of Immunology and Rheumatology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, People's Republic of China.
Purpose: Sepsis-associated liver injury (SALI) leads to increased mortality in sepsis patients, yet no specialized tools exist for early risk assessment. This study aimed to develop and validate a risk prediction model for early identification of SALI before patients meet full diagnostic criteria.
Patients And Methods: This retrospective study analyzed 415 sepsis patients admitted to ICU from January 2019 to January 2022.
ACS Appl Mater Interfaces
January 2025
College of pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, PR China.
This study introduced a hydrogel dressing, termed SODex-gel, which was constructed by establishing Schiff base and hydrogen bonds with the precursors of oxidized dextran (ODex) and succinic dihydrazide (SD)-modified sodium alginate (SD--SA). Through comprehensive and studies, the adhesive properties, self-healing capabilities, hemostatic potential, and wound healing efficacy of the SODex-gel dressing were meticulously evaluated. The H NMR, FTIR, and TGA analyses confirmed the fabrication of the SODex-gel dressing and its constituent elements.
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