Protective effects of fructose-1,6-diphosphate on acute and chronic doxorubicin cardiotoxicity in rats.
The effects of fructose-1,6-diphosphate, an intermediate metabolite of glycolysis, on acute and chronic cardiotoxicity of doxorubicin were investigated in rats. In the acute study, urethane-anaesthetized Wistar female rats treated with 10 mg/kg i.v. doxorubicin developed a widening of the S alpha T segment, an impairment of +dP/dtmax, and tachycardia. Pretreatment with 375 and 750 mg/kg i.p. fructose-1,6-diphosphate prevented the S alpha T segment from widening, whereas only 750 mg/kg i.p. significantly attenuated the heart rate increase. Chronic cardiomyopathy was induced over a 6-week period by weekly doses of 3 mg/kg i.v. doxorubicin, being characterized in vivo by the progressive enlargement of the S alpha T segment and the occurrence of histological alterations and in vitro by a marked impairment of the inotropic response elicited by adrenaline in isolated hearts from treated rats. Concurrent treatment with 150 and 300 mg/kg i.p. fructose-1,6-diphosphate thrice a week for 6 weeks did not lessen the chronic heart damage, whereas 600 mg/kg given i.p. significantly reduced the widening of the S alpha T segment and the severity of histological damage in vivo, as well as significantly improving the contractile responses of hearts in vitro. These findings suggest that the administration of fructose-1,6-diphosphate plays a protective role in the acute and chronic cardiotoxicity of doxorubicin in the rat.
Danesi
R
R
Institute of Medical Pharmacology, Pisa, Italy.
Bernardini
N
N
Marchetti
A
A
Bernardini
M
M
Del Tacca
M
M
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005635:Fructosediphosphates / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006598:Hexosediphosphates / Q000627:therapeutic use*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D004317:Doxorubicin; C029063:fructose-1,6-diphosphate