flavin-adenine-dinucleotide and Cardiomyopathies

Mitochondrial cardiomyopathies are being studied as metabolic diseases of the cardiac muscle which represents a new approach in metabolic studies. The development of mitochondrial diseases is concomited by an impairment in complexes of mitochondrial respiratory chain, which so far could have been possibly studied exclusively on experimental animals. The method of skinned? fibers enables to measure the pathobiochemical processes in mitochondria in a small amount of bioptic myocardial tissue of patients.. The study is aimed at: applying the method of skinned fibers in biopsy of myocardium in patients, trying to localize the impaired loci of the mitochondrial respiratory chains, prospective early and fast assessment of the diagnosis of mitochondrial cardiomyopathy in patients.. The study brings the first information on the possibility of performing more value measurements of mitochondrial respiratory chains per one bioptic sample from the myocardium in patients. The preliminary results indicate to the prospective possibility of early and fast assessment of the diagnosis of mitochondrial cardio(myo)pathies. The presented results require complementary studies involving the development of "mitochondrial medicine".

Topics: Biopsy; Cardiomyopathies; Flavin-Adenine Dinucleotide; Humans; In Vitro Techniques; Mitochondria, Heart; Mitochondrial Myopathies; Myocardium; NAD; Oxygen Consumption; Ubiquinone

In an effort to develop new methods for preventing side effects of chemotherapy, the authors initiated studies to determine whether Adriamycin (doxorubicin) inhibits the metabolism of riboflavin (vitamin B2). Adriamycin has been shown to form a 1:1 stoichiometric complex with riboflavin, as well as to compete for binding to tissue proteins. Adult rats treated with Adriamycin in clinically relevant doses were compared to control animals in ability to convert riboflavin into flavin adenine dinucleotide (FAD), the active flavin coenzyme derivative, in heart, skeletal muscle, liver, and kidney. Rats treated with Adriamycin exhibited diminished formation of carbon 14 (14C)FAD in skeletal muscle to nearly 50% that of controls, and in heart to about 70% to 80% of controls. Under these conditions, (14C)FAD formation in liver and kidney was largely unaffected by Adriamycin. In preliminary studies, riboflavin-deficient animals treated with Adriamycin had accelerated mortality rates compared to those of food restricted controls treated with similar doses of Adriamycin. The data as a whole suggest a potential mechanism for Adriamycin-induced cardiac and skeletal myopathy, i.e., inhibition of synthesis of FAD, a flavin coenzyme which is involved in electron transport, lipid metabolism, and energy generation. These findings in an animal model raise the possibility that defects of riboflavin nutriture, either dietary or drug-induced, may be a determinant of Adriamycin toxicity. Further studies are required to explore the potential for preventing side effects due to Adriamycin by administration of this vitamin.

Topics: Animals; Cardiomyopathies; Doxorubicin; Flavin-Adenine Dinucleotide; Food Deprivation; Kidney; Liver; Male; Muscles; Myocardium; Rats; Riboflavin Deficiency