Integrated single-cell transcriptomics and proteomics elucidate the molecular mechanisms and detoxification strategy of rifampicin-induced hepatotoxicity
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Le résumé fourni par la source
Rifampicin (RIF), a cornerstone drug in tuberculosis treatment, is associated with hepatotoxicity, which represents a significant adverse effect that frequently causes discontinuation of therapy.However, a comprehensive evaluation of the mechanisms underlying RIF-induced hepatotoxicity remains limited, and the identification of highly effective, low-toxicity therapeutic interventions is urgently needed.In this study, we employed a RIF-induced mouse hepatotoxicity model to systematically investigate the cellular and molecular events associated with RIF-induced liver injury.By integrating single-cell RNA sequencing, bulk RNA-seq, and mass spectrometry-based proteomics and metabolomics, we identified region-specific hepatocyte damage characterized by elevated reactive oxygen species (ROS) levels and activation of the fatty acid oxidation pathway.At the molecular level, RIF treatment resulted in the upregulation of pregnane X receptor (PXR) and Cyp3a11, along with the downregulation of key antioxidant genes.Moreover, decreased mTOR expression and increased expression of fatty acid oxidation-related genes including Acox1 and Acaa1b suggested an enhanced oxidative metabolism.Recruitment of macrophages further exacerbated hepatocyte damage.Importantly, Rosmarinic acid (RA) administration was shown to attenuate RIF-induced hepatotoxicity.These findings provide a comprehensive molecular and cellular perspective on RIF-induced hepatotoxicity and suggest the potential clinical application of RA as a therapeutic agent in the management of RIF-induced liver injury.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Integrated single-cell transcriptomics and proteomics elucidate the molecular mechanisms and detoxification strategy of rifampicin-induced hepatotoxicity
- Date Crossref
- 01/01/2026
- Éditeur
- Ivyspring International Publisher
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Southern University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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ShenZhen People’s Hospital pays non établi dans la noticeÉtablissement de santé
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Guangdong Pharmaceutical University pays non établi dans la noticeUniversité ou école supérieure
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TCM-Intigrated Cancer Center of Southern Medical University pays non établi dans la noticeÉtablissement de santé
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Southern Medical University pays non établi dans la noticeUniversité ou école supérieure
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Shandong University of Traditional Chinese Medicine Institute of Acupuncture and Moxibustion pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine Department of Pulmonary and Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
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School of Traditional Chinese Medicine and School of pharmaceutical Sciences Guangdong Basic Research center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases pays non établi dans la noticeUniversité ou école supérieure
Southern University of Science and Technology, ShenZhen People’s Hospital et Guangdong Pharmaceutical University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.