Effect of vitamin A administration on resistance of rat heart against doxorubicin-induced cardiotoxicity and lethality.
The peroxyl radical-scavenging activity of vitamin A has been exploited to obtain protection against peroxidative damages induced in rat heart by administration of an acute dose of doxorubicin (10 mg/kg, in vein). Peroxidative lesions were evaluated by both biochemical and histological assays, 48 hr after the injection of doxorubicin. Heart tissue from rats receiving doxorubicin showed a marked increase of protein carbonyl levels, and of membrane conjugated dienes, as well as a decrease of membrane protein thiols. Abnormal chemistries, including a large increase of the activity of serum lactate dehydrogenase and creatine phosphokinase, an index of the myocardial damage caused by doxorubicin, were also observed. Pretreatment of rats with 25 I.U./kg b.wt. of vitamin A, once a day for 2 days, before injecting doxorubicin, substantially reduced the peroxidative damage to heart lipids and proteins, and markedly lowered the serum values of lactate dehydrogenase and creatine phosphokinase to values close to those of control rats. The significant prevention of doxorubicin-induced cardiomyopathy by vitamin A was evident from the histopathological pattern observed after light microscopy. The dosage of vitamin A useful to obtain the protective effect appears safe and does not injure the liver, as indicated by light microscopy of the tissue. A survival study, carried out by injecting rats with a single injection of 10 mg/kg of doxorubicin, showed that pretreatment with 25 I.U. of vitamin A per kg significantly increased survival rate of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Tesoriere
L
L
Istituto di Chimica Biologica, Universita' di Palermo, Italy.
Ciaccio
M
M
Valenza
M
M
Bongiorno
A
A
Maresi
E
E
Albiero
R
R
Livrea
M A
MA
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D016166:Free Radical Scavengers; D006321:Heart / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000097:blood / Q000494:pharmacology*
D016166:Free Radical Scavengers; D010545:Peroxides; D014801:Vitamin A; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase