Pranoprofen

Pranoprofen inhibits ER stress-induced glucose regulated protein 78 (GRP78) expression, an ER-localized molecular chaperon. Pranoprofen inhibits ER stress-induced CCAAT/enhancer-binding protein homologous protein (CHOP) expression, an apoptotic transcription factor. Pranoprofen alone induces eIF2alpha phosphorylation, which is further increased by ER stress. Pranoprofen inhibits ER stress-induced X-box-binding protein 1 (XBP-1) splicing in the primary cultured glial cells. ^[1] Pranoprofen (0.0625 to 1.0 g/L) has poignant cytotoxicity to human corneal endothelial (HCE) cells, and the extent of its cytotoxicity is dose- and time-dependent. Pranoprofen induces plasma membrane permeability elevation, DNA fragmentation, and apoptotic body formation, proving its apoptosis inducing effect on HCE cells. Pranoprofen above 0.0625 g/L has poignant cytotoxicity on HCE cells in vitro by inducing cell apoptosis, and should be carefully employed in eye clinic. ^[2]

Pranoprofen is orally administered, urinary and fecal excretions of the radioactivity within 3 days are 81.1% and 18.7% of the dose in mice, 51.5% and 39.4% in rats, 81.8% and 9.0% in guinea pigs, and 93.2% and 3.6% in rabbits, respectively. ^[3] Pranoprofen is excreted in the urine exclusively in the form of pranoprofen glucuronide in rabbit. Pranoprofen, especially the R(-)-isomer, is significantly distributed in the kidney of rabbit. ^[4] Pranoprofen has a preference for glucosidation rather than glucuronidation in mice at low doses in spite of having a higher capacity of glucuronidation. ^[5]