Investigation of doxorubicin tissue toxicity: does amifostine provide chemoprotection? An experimental study.
This experimental animal study of 12-weeks' duration, involving Wistar rats, tested the possible chemoprotection of Doxorubicin (adriamycin), cardiomyopathy and other toxicities by Amifostine. One hundred and five animals were divided into 3 groups: Groups A, B and C, which had Doxorubicin, simultaneous Doxorubicin and Amifostine treatment and normal saline for control, respectively. Treatment was administered once weekly for 12 consecutive weeks. The doses of each drug were appropriately calculated on the basis of other experiments in the literature and given in analogous dosage to human kilograms of body weight. Euthanasias and autopsies of six animals at a time from each animal group were performed on weeks 3, 6, 8, 10 and 12. The blood, heart, lung, liver, aorta, thymus, spleen, kidneys, adrenals, testis and ovaries and muscle and lipoid tissue were examined macroscopically and microscopically. Biochemical liver and kidney examinations, full blood count and serum lipids were examined before and during the weeks of treatment and autopsies. Increased cholesterol and triglycerides from the 6th week towards the end of the experiment and a gradual increase in cardiomyopathy were found, particularly in Group A. The findings were similar in Group B, except for the timing (the increase of serum lipids and the serious cardiac lesions were delayed by two weeks). No abnormalities were detected in the controls, Group C. In conclusion, Amifostine does not seem to be cardioprotective when administered with Doxorubicin, since it only delays the onset of cardiac lesions. In in vitro testing, Amifostine was found to be a scavenger of the oxygen-free radicals which are produced by Doxorubicin.
Rigatos
Sotiris K
SK
Hippokration Hospital, 2nd Medical Division, University of Athens School of Medicine, Greece.
Stathopoulos
George P
GP
Dontas
Ismene
I
Perrea-Kotsarelis
Despina
D
Couris
Ephrosini
E
Karayannacos
Panayotis E
PE
Deliconstantinos
George
G
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000903:Antibiotics, Antineoplastic; D017382:Reactive Oxygen Species; D014280:Triglycerides; D004317:Doxorubicin; D002784:Cholesterol; D004999:Amifostine