Amifostine (WR2721) Confers DNA Protection to Cisplatin-Treated Murine Peripheral Blood Leukocytes

Abstract

Amifostine [S-2-3-aminopropil amino ethyl phosphorotioic acid], a modulator agent for antineoplastic drugs involved in free radicals generation has given controversial results in cisplatin treated leukocytes in vitro . We have evaluated the amifostine protection over leukocytes in vivo , using comet assay. Groups of five OF1 male mice were given one of three doses of amifostine (56, 105 and 200 mg/Kg) after a cisplatin single injection (10 mg/Kg). Serum malonyldialdehide levels, catalase and superoxide dismutase activity were also evaluated. Amifostine showed significant DNA protection (p< 0.01) at the two lower doses evaluated. Malonyldildehide decreased in all amifostine treatments with respect to cisplatin while antioxidant enzyme activities remained unchanged. However, DNA migration increased with the highest amifostine dose; in fact highest dose of amifostine did no protect damage caused by cisplatin this result have implications on amifostine treatment schedules in clinical practice.