Flurbiprofen, a non-steroid anti-inflammatory agent, protects cells against hypoxic cell radiosensitizers in vitro

Abstract

Summary.-Overnight exposure of Chinese hamster cells (V79-753B) to 5 x 10-5M flurbiprofen (2-(2-fluoro-4-biphenyl)propionic acid) in vitro reduced the cytotoxic effects of misonidazole, 1-methyl -4-nitro -5 -phenoxysulphonylimidazole (NSC 38087) and nitrofurantoin, both in air and in hypoxia at 37°C. Flurbiprofen did not alter the cells' uptake of 14C-misonidazole, nor did it affect the radiosensitivity of aerobic or anaerobic cells, or the degree of hypoxic-cell radiosensitization produced by the sensitizers. When flurbiprofen-treated cells were exposed to melphalan there was no protection against cytotoxicity. These data suggest that flurbiprofen may inhibit the catabolism of radiosensitizers to toxic products and indicate the need to examine whether it will protect against misonidazole-induced toxicity in vivo.

Renal elimination of the hypoxic cell radiosensitizer misonidazole in wistar rats: influence of some drugs on its excretion

“…Other drugs are being examined, therefore, in an attempt to reduce the toxicity of Miso without affecting its radiosensitization properties, such a non steroidal anti-inflammatory agent, flurbiprofen (17).…”

Phenylalanine conjugated supramolecular hydrogels developed from the mafenide and flurbiprofen multidrug for biological applications

“…[48][49][50][51] Hence, to avoid the usually encountered issues of synthesis, cytotoxicity, and biodegradability involving drug-loaded vehicles, herein, we have tried to employ salt-based multidrug systems having primary ammonium monocarboxylate (PAM) synthons with an additional gel-inducing amide hydrogenbonding supramolecular functionality and hydrophobic moieties. We considered a well-known US Food and Drug Administration (FDA)-approved NSAID, flurbiprofen (FLR), 52 which is basically used to reduce swelling, pain and joint stiffness from arthritis. As the amide functionality is known to impart gelation through its extended hydrogen-bonded networks (HBNs), 53 we first decided to synthesize covalent bioconjugates of flurbiprofen with two selected amino acids L-phenylalanine (PHE) and L-alanine (ALA) having hydrophobic side chains.…”