Protective effect of flavonoids on doxorubicin-induced cardiotoxicity.
We have examined the effect of alpha G-Rutin and luteolin on doxorubicin (DOX) toxicity in mice. In the heart, the lipid peroxide level, increased to 1.5 times of the normal level induced by DOX, decreased to the normal level after treatment with alpha G-Rutin or luteolin (i.p.). Glutathione peroxidase (GSHpx) activity, decreased to 73% of normal activity after DOX treatment, was shown to recover by the combined flavonoids. The lipid peroxide level in bone marrow cells increased to 5.9 times of the normal level by DOX treatment, whereas this level in the extra bone marrow cells did not change by treatment with DOX. The combination of alpha G-Rutin and luteolin with DOX significantly inhibited the DOX induced-increment of the lipid peroxide level in bone marrow cells. Flavonoids have also reduced the effect of DOX toxicity by oral administration. It is suggested that it is possible to reduce DOX toxicity by the intake of food including flavonoids. In NADPH-dependent lipid peroxidation, alpha G-Rutin and luteolin showed concentration-dependent inhibition. Therefore, we considered that the reduction effect of DOX toxicity by flavonoids was caused by antioxidative action and other effect of the flavonoids.
Sadzuka
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan.
Sugiyama
T
T
Shimoi
K
K
Kinae
N
N
Hirota
S
S
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001853:Bone Marrow / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003402:Creatine Kinase / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D047311:Luteolin; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D005419:Flavonoids; D008054:Lipid Peroxides; D012431:Rutin; D004317:Doxorubicin; D005979:Glutathione Peroxidase; D009247:NADH, NADPH Oxidoreductases; D003402:Creatine Kinase; D047311:Luteolin