{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:01:46Z","timestamp":1787313706475,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Trovafloxacin is a quinolone antibiotic drug with broad\u2010spectrum activity, which was withdrawn from a global market relatively soon after approval because of serious liver injury. The characteristics of trovafloxacin\u2010induced 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\u2010associated 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\u20104 (FLC\u20104) cells, and THP\u20101 cells (human monocyte cell line) were used for the detection of inflammasome activation. The supernatant from the incubation of trovafloxacin with FLC\u20104 cells for 7\u00a0days increased caspase\u20101 activity and production of IL\u20101\u00df by THP\u20101 cells. In the supernatant of FLC\u20104 cells that had been incubated with trovafloxacin, heat shock protein (HSP) 40 was significantly increased. Addition of a cytochrome P450 inhibitor to the FLC\u20104 cells prevented the release of HSP40 from the FLC\u20104 cells and inflammasome activation in THP\u20101 cells by the FLC\u20104 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\u2010related liver injury.<\/jats:p>","DOI":"10.1002\/jat.4585","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T22:50:30Z","timestamp":1706655030000},"page":"846-852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Reactive metabolite of trovafloxacin activates inflammasomes: Implications for trovafloxacin\u2010induced liver injury"],"prefix":"10.1002","volume":"44","author":[{"given":"Saori","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapeutics and Toxicology, Faculty of Pharmacy Osaka Medical and Pharmaceutical University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of 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