Efficiency of amifostine as a protection against doxorubicin toxicity in rats during a 12-day treatment.
BACKGROUND
Our purpose was to determine the effects of amifostine, a cytoprotective agent, on doxorubicin tolerance and cardiotoxicity in rats.


METHODS
Male Wistar rats were treated every other day with an intraperitoneal injection of amifostine or saline 30 minutes before intraperitoneal injection of doxorubicin or saline. Weight change was recorded, and contractile function was evaluated after 11 injections by means of the isolated heart.


RESULTS
Weight evolution and cardiac function were significantly improved by 7 and 20 mg/kg amifostine (p < 0.001) but not by 50 mg/kg. The final weight were: controls 349 +/- 16 g; doxorubicin alone 258 +/- 54 g; with amifostine: 7 mg/kg 314 + 28 g; 20 mg/kg 312 +/- 32 g; 50 mg/kg 250 +/- 34 g. Left ventricular developed pressure were: controls 137 +/- 15 mmHg; doxorubicin alone 119 +/- 20 mmHg; with amifostine: 7 mg/kg 140 +/- 20 mmHg; 20 mg/kg 137 +/- 25 mmHg; 50 mg/kg 124 +/- 20 mmHg.


CONCLUSIONS
Seven and 20 mg/kg amifostine protected rats from the toxicity of doxorubicin at the cumulative dose of 18 mg/kg during a 12-day treatment, with regard to weight loss and heart contraction.
Nazeyrollas
P
P
Laboratoire de Pharmacologie, Faculté de Médecine, Service de Cardiologie, CHU de Reims, 51092 Reims, France. pnazey@hexanet.fr
Frances
C
C
Prevost
A
A
Costa
B
B
Lorenzato
M
M
Kantelip
J P
JP
Elaerts
J
J
Millart
H
H
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D004999:Amifostine