BACKGROUND: Infliximab-induced hepatotoxicity is reported in several case studies involving patients with inflammatory bowel disease (IBD) and a direct hepatotoxic effect has been proposed. OBJECTIVE: The aim of this study was to determine the direct in vitro toxicity of infliximab. As a proof of principle the in vitro toxicity of thiopurines and methotrexate was also determined. METHODS: Cell survival curves and the half maximal inhibitory concentrations (IC(50)) were obtained after 24, 48 and 72 h of incubation in HepG2 cells with the IBD drugs azathioprine, 6-mercaptopurine, 6-thioguanine, methotrexate or infliximab by using the WST-1 cytotoxicity assay. RESULTS: No in vitro hepatotoxicity in HepG2 cells was seen with infliximab, while concentration-dependent cytotoxicity was observed when HepG2 cells were incubated with increasing concentrations of azathioprine, 6-mercaptopurine and 6-thioguanine. CONCLUSION: Infliximab alone or given in combination with azathioprine showed no direct hepatotoxic effect in vitro, indicating that the postulated direct hepatotoxicity of infliximab is unlikely.
BACKGROUND:Infliximab-induced hepatotoxicity is reported in several case studies involving patients with inflammatory bowel disease (IBD) and a direct hepatotoxic effect has been proposed. OBJECTIVE: The aim of this study was to determine the direct in vitro toxicity of infliximab. As a proof of principle the in vitro toxicity of thiopurines and methotrexate was also determined. METHODS: Cell survival curves and the half maximal inhibitory concentrations (IC(50)) were obtained after 24, 48 and 72 h of incubation in HepG2 cells with the IBD drugs azathioprine, 6-mercaptopurine, 6-thioguanine, methotrexate or infliximab by using the WST-1 cytotoxicity assay. RESULTS: No in vitro hepatotoxicity in HepG2 cells was seen with infliximab, while concentration-dependent cytotoxicity was observed when HepG2 cells were incubated with increasing concentrations of azathioprine, 6-mercaptopurine and 6-thioguanine. CONCLUSION:Infliximab alone or given in combination with azathioprine showed no direct hepatotoxic effect in vitro, indicating that the postulated direct hepatotoxicity of infliximab is unlikely.
Authors: A Bruccoleri; R Gallucci; D R Germolec; P Blackshear; P Simeonova; R G Thurman; M I Luster Journal: Hepatology Date: 1997-01 Impact factor: 17.425
Authors: F D'Auria; P Rovere-Querini; M Giazzon; P Ajello; E Baldissera; A A Manfredi; M G Sabbadini Journal: J Intern Med Date: 2004-03 Impact factor: 8.989
Authors: Fotios S Fousekis; Vasileios I Theopistos; Konstantinos H Katsanos; Epameinondas V Tsianos; Dimitrios K Christodoulou Journal: Gastroenterology Res Date: 2018-04-07
Authors: Mark M T J Broekman; Hennie M J Roelofs; Dennis R Wong; Mariska Kerstholt; Alex Leijten; Frank Hoentjen; Wilbert H M Peters; Geert J A Wanten; Dirk J de Jong Journal: Cell Biol Toxicol Date: 2015-04-28 Impact factor: 6.691