In vitro antioxidant properties of amifostine (WR-2721, Ethyol)

Abstract

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(-).

Doxorubicin-Induced Oxidative Injury of Cardiomyocytes - Do We Have Right Strategies for Prevention?

“…It is also known that amifostine is negative charged thiol and this protector accumulates within the mitochondria and around DNA, explaining higher protective amifostine potential for them than neutral or positive charged thiols, especially since some studies using perfused rat hearts showed that DOX is localized primarilly to the nucleus and mitochondria of the cell (Berthiaume & Wallace, 2007). It was also shown that both amifostine and WR-1065 significantly reduced DOX-induced heart cell toxicity, measured by ATP content normalised to total cellular protein (Marzatico et al, 2000). This finding can also be explained by effective protection of mitochondria, as in our study, since oxidative phosphorylation is one of the functions of this organelae which provides a substantial portion of the ATP needed to meet energy demands in the heart.…”

“…Moreover, a mean cardiac damage (MCD) score, obtained by histopathological analysis, in amifostine-pretreated rats was significantly reduced compared with unprotected animals, on both days 7 and 28 after WBI. It has been supposed for a long time, according to data derived from the experiments with irradiated animals, that once inside the cell, protective effects of WR-1065 appear to be mediated by scavenging free radicals, hydrogen donation, induction of cellular hypoxia, the liberation of endogenous nonprotein sulfhydrils (mainly glutathione) from their bond with cell proteins, the formation of mixed disulphides to protect normal cells, etc (Brown, 1967;Grdina et al, 1995;Smoluk et al, 1988;Spencer & Goa, 1995 Marzatico et al, (2000) showed that amifostine scavenging activity is exerted mainly against highly reactive OH. , the most dangerous reactive oxygen species from a biological point of view (Marzatico et al, 2000).…”

Oxidative study of patients with total body irradiation: effects of amifostine treatment

“…It is known that the in vitro amifostine antioxidant activity shows scavenging activity against lipoperoxidation and against the highly reactive hydroxyl radical. 15 Pharmacokinetic data show that amifostine is cleared in the patient's plasma with a half-life of about 10 min, and that the active drug concentration in the blood cell fraction is similar to that of plasma. 16 We have used amifostine to prevent toxicity related to TBI, and compared these results with similar patients not receiving the drug, in a retrospective analysis.…”

Aminothiol WR1065 induces differential gene expression in the presence of wild-type p53

“…Phosphorylated WR2721 is converted by alkaline phosphatase to the active aminothiol WR1065 (Calabro-Jones et al, 1985) upon crossing plasma membranes. Overall, WR1065 has been shown to protect cells from oxidative injury (Polla et al, 1990), likely due to its ability to scavenge highly reactive OH À radicals (Marzatico et al, 2000). The protective effect of WR1065 may also be due in part to its ability to prevent the rise in intracellular Ca 2 þ , which occurs in response to oxidative injury (Polla et al, 1990).…”