Key result
Adriamycin significantly increases FAD biosynthesis from riboflavin in rat skeletal muscle.
Why the study?
Adriamycin interacts with flavin derivatives and competes with flavin coenzymes, but its effect on FAD biosynthesis in skeletal muscle was unclear.
Adriamycin inhibits FAD biosynthesis in skeletal muscle, suggesting a metabolic mechanism that may contribute to adriamycin-induced myopathy.
May implicate FAD pathway disruption in adriamycin myopathy; leaves open relevance to human cardiac or skeletal toxicity.
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.
No takes yet. Share an insight, caveat, or question.
Raiczyk et al. (1988) studied Flavin metabolism in skeletal muscle. Adriamycin vs. Pair-fed controls was evaluated on [14C]FAD formation from [14C]riboflavin. Adriamycin administration at cumulative doses of 12 to 30 mg/kg significantly increased [14C]FAD formation from [14C]riboflavin in rat skeletal muscle compared to pair-fed controls.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: