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Mechanism of non-steroidal anti-androgen-induced liver injury: Reactive metabolites of flutamide and bicalutamide activate inflammasomes.
Get PDFFlutamide is a non-steroidal anti-androgen agent, which is mainly used for the treatment of prostate cancer. Flutamide is known to cause severe adverse events, which includes idiosyncratic liver injury. However, details of the mechanism of these adverse reactions have not been elucidated. We investigated whether flutamide induces the release of damage-associated molecular patterns (DAMPs) that activate inflammasomes. We also tested bicalutamide, enzalutamide, apalutamide, and darolutamide for their ability to activate inflammasomes in differentiated THP-1 cells. The supernatant from the incubation of flutamide and bicalutamide with human hepatocarcinoma functional liver cell-4 (FLC-4) cells increased caspase-1 activity and production of IL-1ß by differentiated THP-1 cells. In the supernatant of FLC-4 cells with flutamide and bicalutamide, the heat shock protein (HSP) 40 or 60 was significantly increased. Addition of a carboxylesterase or a CYP inhibitor to the FLC-4 cells prevented release of HSPs from the FLC-4 cells. These results suggested that the reactive metabolites of flutamide and bicalutamide 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 flutamide or bicalutamide, which in some patients, can cause immune-related adverse events.journal articl
The flexion–extension gap is predictive of patient-reported outcome measures after cruciate-retaining total knee arthroplasty
Get PDF大阪医科薬科大学博士（医学）2023doctoral thesi
miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia
Get PDF大阪医科薬科大学博士（医学）2022doctoral thesi
Association between serum biomarkers and peripheral neuropathy in microscopic polyangiitis
Get PDF大阪医科薬科大学博士（医学）2022doctoral thesi
サイクリン依存性キナーゼ５阻害剤であるロスコビチンが,ラットの挫滅後の視神経に対して,タウ蛋白のリン酸化と網膜神経節細胞死を抑制する過程の検討
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