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Trovafloxacin is a quinolone antibiotic drug with broad‐spectrum activity, which was withdrawn from a global market relatively soon after approval because of serious liver injury. The characteristics of trovafloxacin‐induced liver injury are consistent with an idiosyncratic reaction; however, the details of the mechanism have not been elucidated. We examined whether trovafloxacin induces the release of damage‐associated molecular patterns (DAMPs) that activate inflammasomes. We also tested ciprofloxacin, levofloxacin, gatifloxacin, and grepafloxacin for their ability to activate inflammasomes. Drug bioactivation was performed with human hepatocarcinoma functional liver cell‐4 (FLC‐4) cells, and THP‐1 cells (human monocyte cell line) were used for the detection of inflammasome activation. The supernatant from the incubation of trovafloxacin with FLC‐4 cells for 7 days increased caspase‐1 activity and production of IL‐1ß by THP‐1 cells. In the supernatant of FLC‐4 cells that had been incubated with trovafloxacin, heat shock protein (HSP) 40 was significantly increased. Addition of a cytochrome P450 inhibitor to the FLC‐4 cells prevented the release of HSP40 from the FLC‐4 cells and inflammasome activation in THP‐1 cells by the FLC‐4 supernatant. These results suggest that reactive metabolites of trovafloxacin can cause the release of DAMPs from hepatocytes that can activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by trovafloxacin, which, in some patients, can cause immune‐related liver injury. Trovafloxacin is a quinolone antibiotic drug, which was withdrawn from a global market because of serious liver injury. We investigated whether trovafloxacin or its reactive metabolites induces the release of damage‐associated molecular patterns (DAMPs) that activate inflammasomes. This study suggested that the reactive metabolites of trovafloxacin can cause the release of DAMPs from hepatocytes and activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by trovafloxacin. [ABSTRACT FROM AUTHOR]

TBI is a leading cause of death and disability in young people and older adults worldwide. There is no gold standard treatment for TBI besides surgical interventions and symptomatic relief. Post-injury infections, such as lower respiratory tract and surgical site infections or meningitis are frequent complications following TBI. Whether the use of preventive and/or symptomatic antibiotic therapy improves patient mortality and outcome is an ongoing matter of debate. In contrast, results from animal models of TBI suggest translational perspectives and support the hypothesis that antibiotics, independent of their anti-microbial activity, alleviate secondary injury and improve neurological outcomes. These beneficial effects were largely attributed to the inhibition of neuroinflammation and neuronal cell death. In this review, we briefly outline current treatment options, including antibiotic therapy, for patients with TBI. We then summarize the therapeutic effects of the most commonly tested antibiotics in TBI animal models, highlight studies identifying molecular targets of antibiotics, and discuss similarities and differences in their mechanistic modes of action. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease that occurs globally. Treatment of TB has been hindered by problems with multidrug-resistant strains (MDR-TB). Fluoroquinolones are one of the main drugs used for the treatment of MDR-TB. The success of therapy can be influenced by genetic factors and their impact on pharmacokinetic parameters. This review was conducted by searching the PubMed database with keywords polymorphism and fluoroquinolones. The presence of gene polymorphisms, including UGT1A1 , UGT1A9 , SLCO1B1 , and ABCB1 , can affect fluoroquinolones pharmacokinetic parameters such as area under the curve (AUC), creatinine clearance (C Cr ), maximum plasma concentration (C max ), half-life (t 1/2 ) and peak time (t max ) of fluoroquinolones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Annisa, Barliana, Santoso and Ruslami.)

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. • Drug-induced liver injury (DILI) is an adverse drug reaction and its prediction remains extremely challenging. Further, drug-induced innate immune response such as inflammation can amplify liver tissue damage. • In this study, we found that the proinflammatory M1 macrophage is mainly activated, promoting trovafloxacin (TVX)-induced liver injury by the release of high levels of proinflammatory cytokines (TNF-α). • Further, the transcriptome in liver macrophages exposed to TVX suggests candidate biomarker genes to improve the early detection of immunological DILI in the absence of diagnostic DILI biomarkers. [ABSTRACT FROM AUTHOR]