The Protective Effects of Amifostine on Adriamycin-Induced Acute Cardiotoxicity in Rats

Abstract

Free oxygen radicals and lipid peroxidation are responsible for adriamycin-induced cardiotoxicity. Amifostine is a scavenger of free radicals and may function as a selective cytoprotective agent. The aim of this study was to investigate the effects of amifostine on adriamycin-induced lipid peroxidation and the levels of protective enzymes in the heart. Male Wistar rats were randomly allocated to three groups: pretreated, untreated, and control (n = 10 in each group). Rats were pretreated with an intraperitoneal injection of amifostine (200 mg/kg) 30 min before the injection of adriamycin. The pretreated rats were given an intraperitoneal injection of adriamycin (10 mg/kg) and were sacrificed after 72 h. Likewise, rats received intraperitoneal injection of adriamycin (untreated) or saline (control). The hearts were removed for the analyses of malondialdehyde (MDA), reduced glutathione (GSH) and catalase. MDA levels were increased ( p < 0.005) in the heart tissues of untreated rats compared to control, while GSH and catalase levels were decreased ( p < 0.05 and p < 0.001, respectively) in untreated animals. In amifostine-preatreated group, MDA levels were lower ( p < 0.01), and GSH and catalase levels were higher ( p < 0.05 for both) than the untreated group. GSH levels were even higher in the amifostine-pretreated group compared to control ( p < 0.01), although catalase levels were significantly lower in the pretreated group ( p < 0.05). These results indicate that amifostine decreases adriamycin-induced lipid peroxidation and increases the levels of the protective enzymes in the heart tissue. Therefore, amifostine may ameliorate the adriamycin-induced acute cardiotoxicity.

The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats

“…The effects of doxorubicin on GSH and protective enzymes such as catalase, Gpx and SOD are controversial a :p < 0.001 as compared to control group, b :p < 0.05 as compared to control group, c :p < 0.05 as compared to MITO-2.5 group, d :p < 0.001 as compared to MITO-2.5 group, e :p < 0.01 as compared to control group, f :p < 0.005 as compared to MITO-2.5 group, g :p < 0.005 as compared to control group, h :p < 0.001 as compared to AMI group [9,11,12,33,34]. Although MITO induced lipid peroxidation and the generation of free oxygen radicals in liver microsomes [3,8,18], there are only a few experimental studies in which these effects in the heart are demonstrated [22,23].…”

“…Catalase, SOD and Gpx play critical roles in protecting the myocardium from lipid peroxidation and free oxygen radicals under oxidative damage. It was detected in some experimental studies that doxorubicin and idarubicin decreased GSH, catalase, Gpx, and SOD levels in the heart tissue [9,11,37,38]. However, over-expression of catalase and Mn-SOD activities were detected after doxorubicin administration.…”

“…Although myocardial adrenergic dysfunction including down-regulation of myocardial β-adrenergic receptors, intracellular calcium overload, induction of apoptosis, and release of cardiotoxic cytokines such as tumor necrosis factor-alpha and interleukin-2 may play a role in the pathogenesis of anthracycline-induced cardiotoxicity, focus in recent years has been on free oxygen radicals and lipid peroxidation [2,3,[6][7][8][9][10].…”

“…AMI has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies [9,[11][12][13][14][15][16]. AMI protects the myocardium, inhibiting lipid peroxidation, apoptosis and the production of free oxygen radicals [9,11,12,15,17].…”

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

“…Protection from cisplatin nephrotoxicity and ototoxicity has been shown, as well as protection of peripheral neural tissue from cisplatin, paclitaxel, vincristine and vinblastine toxicity. However, data concerning amifostine efficacy in preventing the toxic effects of DOX are still insufficient (Bolaman et al, 2005;Dobric et al, 1998;Dragojevic-Simic et al, 2004;Nazeyrollas et al, 1999;Potemski et al, 2006). As previously mentioned, amifostine uptake has been documented to be relatively high in normal tissues compared with experimental tumors.…”