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Trovafloxacin is a quinolone antibiotic drug with broad‐spectrum activity, which was withdrawn from a global market relatively soon after approval because of serious liver injury.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 Trovafloxacin is a quinolone antibiotic drug, which was withdrawn from a global market because of serious liver injury.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]

Background/aim: In clinical practice, platinum-based systemic chemotherapy works to shrink pelvic lymph nodes. Intra-arterial (IA) bolus infusion may result in more favorable results than systemic chemotherapy. In the present study, we investigated the distribution of cisplatin administrated by IA infusion in varying organs, specifically focusing on the node tissue, in comparison with the intravenous (IV) route., Materials and Methods: Under anesthesia, cisplatin 0.42 mg/body was administrated by IA or IV infusion in rats to mimic a balloon-occluded arterial infusion model used in clinical practice. The kidney, bladder, lymphatic tissue, and peripheral blood were extracted to analyze the amount of cisplatin by inductively coupled plasma-mass spectrometry., Results: Concertation of cisplatin by IA infusion was higher than that by the IV route in the peripheral blood and kidney. IA infusion led to a significantly high concentration of cisplatin in the bladder compared to IV infusion (1.3±0.452 vs. 0.2 ppb/mg ± 0.055, p=0.050). Furthermore, the IA method led to an extremely high concentration of cisplatin in the lymphatic tissue compared to the IV method (0.1±0.036 vs. 13.3±5.36, p=0.048)., Conclusion: High cisplatin accumulation in the lymphatic tissue and bladder by IA administration may have a potential role for treating patients with node-positive bladder cancer., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)