The effect of doxorubicin and its analogue mitoxantrone on cardiac muscle and on serum lipids: an experimental study.
This experimental study compares the toxic effect of the two cytotoxic drugs, doxorubicin and mitoxantrone, on cardiac muscle and on serum lipids. The cardiotoxicity of doxorubicin due to the cumulative effect of repeated administration is known. A relative compound, mitoxantrone, is a member of the androstenedione class of synthetic antitumor agents and its chemical structure, based on a quinone ring, is similar to that of doxorubicin. Doxorubicin has wide application in cancer medicine but its dose-limited cardiac effect creates the need for a substitute compound. Mitoxantrone, also an effective agent, may be able to cover this need. Three groups of 35 Wistar rats were used during this experimental study of 12 weeks' duration. Drugs at a certain calculated dose were administered once weekly. Group A animals were treated with doxorubicin, Group B with mitoxantrone and Group C, the controls, with normal saline. Six animals per group were autopsied after euthanasia in the 3rd, 6th, 8th, 10th and 12th weeks. Cardiac muscle, liver and other organs, plus blood, were removed for macro- and microscopical, and biochemical tests. Our results showed that there was a cumulative toxic effect of doxorubicin (adriamycin) on cardiac muscle starting in the 6th week which gradually increased to Grade III lesions by the 10th and 12th weeks. In parallel, an increase in serum lipids, mainly cholesterol and triglycerides was observed. Mitoxantrone-treated animals showed moderate cardiotoxic lesions (but not cumulative) and no increase in serum lipids. In vitro testing of oxygen-free radical production showed high production by doxorubicin and very low production by mitoxantrone. Thus, mitoxantrone appears to be safer than doxorubicin.
Koutinos
George
G
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
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D008297:Male; D008942:Mitoxantrone / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008055:Lipids; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D008942:Mitoxantrone