Trovafloxacin drives inflammation-associated drug-induced adverse hepatic reaction by changing macrophage polarization.
Toxicol In Vitro
; 82: 105374, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35537566
ABSTRACT
Drug-induced liver injury (DILI) is an adverse hepatic reaction and a serious concern for public healthcare systems and pharmaceutical companies. DILI is frequently caused by a combination of direct toxic stresses and subsequent immune damage to hepatocytes. However, little is known about the mechanism by which drugs facilitate the activation of the innate immune system. Here, we aimed to decipher the inflammatory events in trovafloxacin (TVX)-induced reactions using liver macrophages. We showed that proinflammatory M1-like macrophages mainly contributed to hepatotoxicity mediated by TVX, a DILI drug. Additionally, transcriptome results showed that the interferon type I pathway, cytokines, and apoptosis pathway were involved in the initiation of synergistic effects resulting in TVX-induced liver injury. We hypothesized that DILI drugs could drive liver injury by altering the activation and phenotype of hepatic macrophages. Furthermore, drug treatment-induced transcriptional changes such as Traf1 and 2, Socs3, and Hbegf in macrophage polarization could be used to assess drug-specific immune-mediated reactions. Therefore, we proposed that transcriptional change in the genes related to macrophage polarization index could be an indicator to reflect the severity of DILI in a preclinical setting during drug development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
/
Doença Hepática Induzida por Substâncias e Drogas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Toxicol In Vitro
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article