Effects of nimesulide and its metabolites or manufacturing intermediates on the viability and growth of the human hepatoma HepG2 cell line.
Hepatitis and fulminant hepatic failure have, infrequently, been associated with nimesulide. To establish if nimesulide or its analogues have direct cytotoxic activity on liver cells, experiments were undertaken to investigate the effects of nimesulide and its principal metabolites and production intermediates on the viability and growth of the human hepatoma cell line, HepG2, in vitro. The parent drug, metabolites or production intermediates as well as formulations of nimesulide were incubated for 6-48 hr with HepG2 cells and the extent of toxicity determined using the mitochondrial selective redox dye 3-4,5-dimethylthazol-2-yl)-2,4-diphenyl tetrazolium bromide (MTT). The results showed that there was no appreciable cytotoxic activity exhibited by nimesulide and its principle metabolites or production intermediates on HepG2 cells.
Rainsford
K D
KD
Biomedical Research Centre, Divisions of Biomedical Sciences and Chemistry, Sheffield Hallam University, UK. K.D.Rainsford@shu.ac.uk
Seabrook
R W
RW
Spencer
S
S
Hewson
A T
AT
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C012655:nimesulide