The protective effects of amifostine on adriamycin-induced acute cardiotoxicity in rats.
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.
Bolaman
Zahit
Z
Department of Internal Medicine, Division of Hematology, Adnan Menderes University Medical School, Aydin, Turkey. zahitb@yahoo.com
Cicek
Ceyhan
C
Kadikoylu
Gurhan
G
Barutca
Sabri
S
Serter
Mukadder
M
Yenisey
Cigdem
C
Alper
Gulinaz
G
D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute
D020011:Protective Agents; D008315:Malondialdehyde; D004317:Doxorubicin; D002374:Catalase; D005978:Glutathione; D004999:Amifostine