Inhibition of flavin metabolism by adriamycin in skeletal muscle.
Adriamycin (ADR), a potent antineoplastic agent, has been shown to interact with flavin derivatives and to compete with flavin coenzymes for their respective binding sites on flavin-containing enzymes. The present investigation determined that ADR administration inhibited flavin adenine dinucleotide (FAD) biosynthesis from riboflavin in rat skeletal muscle in a dose-related manner compared to results in pair-fed controls. Five groups of adult Holtzman rats of both sexes were given twice daily intraperitoneal injections of ADR for 3 days, representing cumulative doses of 6, 12, 18, 24, and 30 mg/kg body weight. At the cumulative dose of 6 mg/kg, there was no significant effect, but at 12, 18, 24, and 30 mg/kg levels significant increases in [14C]FAD formation from [14C]riboflavin occurred. ADR-induced myopathy may be due, at least in part, to inhibition of FAD formation, ultimately leading to changes in energy metabolism and oxidative capacity.
Raiczyk
G B
GB
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pinto
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D005182:Flavin-Adenine Dinucleotide; D004317:Doxorubicin