Key words Amifostine
Springer Online Journal Archives 1860-2000
Abstract Purpose: Amifostine (WR-2721), a phosphorylated aminothiol pro-drug which is an analogue of cysteamine, is a selective cytoprotective agent for normal tissues from the toxicities associated with chemotherapy and irradiation. Despite a growing number of reports strongly supporting amifostine's clinical efficacy, few authors have focused on the biochemical basis of amifostine's antioxidant activity. Methods: We report on amifostine's free-radical scavenging activity against superoxide (O2˙−), hydroxyl (OH−) and lipoperoxyl radicals in an in vitro model, using pure chemical systems. Amifostine was dephosphorylated to its active metabolite, WR-1065, by adding 10% non-heat-inactivated serum; different amifostine concentrations (1, 10, 50, 100 μM and 200 μM) and pH conditions (pH 5, 7.4 and 9) were tested. Results: Independent of the concentration, amifostine exhibited no major activity against O2˙− ions, neither did any pH variations in the experimental model provide any scavenger effects of the drug against O2˙− radicals. On the other hand, the protective effect of amifostine against OH− radicals was confirmed, yielding an EC50 of 255 μM at pH 7.4 and 230 μM at pH 5. Finally, amifostine exhibited scavenging activity against spontaneous lipoperoxidation, but no apparent antioxidant effect on iron ascorbate-induced lipoperoxidation. Conclusions: With this in vitro study, we are able to confirm the scavenging activity of the chemo- and radioprotector amifostine, whose activity seems to be particularly important from a biological point of view, since it is exerted mainly against highly reactive OH−.
Type of Medium: