New approaches to the possible prevention of side effects of chemotherapy by nutrition

Abstract

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.

Screening of Antioxidants from Medicinal Plants for Cardioprotective Effect against Doxorubicin Toxicity

“…The generated doxorubicin free radicals cause DNA breaks and lipid peroxidation (Chautan et al 1992;Dziegiel et al 2002;Quiles et al 2002). Cardiac tissue is sensitive to oxidative damage because of its highly oxidative metabolism and lower antioxidant defenses in this organ compared with others (Pinto et al 1986;Shug 1987). The high level of oxidative stress during chemotherapy may overcome the antioxidant defenses in cardiac tissue leading to toxicity.…”

Dose-Dependent Amelioration of Gentamicin-Induced Nephrotoxicity in Adult Swiss Albino Rats by Vitamin B-complex - A Preliminary Study

“…Depletion of some of these ingredients has been suggested to contribute to gentamicin toxicity 7,8,9 . This study was carried out as a preliminary evaluation of the influence of B-complex, administered intramuscularly, on the nephrotoxicity of gentamicin.…”

Inhibition of Riboflavin Metabolism in Cardiac and Skeletal Muscles of Rats by Quinacrine and Tetracycline

“…In addition, the phenothiazine derivative, chlorpromazine, antagonizes flavin biosynthesis [7] and has antimalarial properties [8]. Our laboratory has previously demonstrated that adriamycin, an anthracycline antineoplastic agent with close similarities to tetracycline, inhibits the conversion of riboflavin to flavin adenine dinucleotide (FAD) particularly in heart and skeletal muscle of rats [9].…”

“…Studies in our laboratory have shown that flavin metabolism in cardiac and skeletal muscle is particularly sensitive to the effects of drugs containing tri-and tetracyclic ring derivatives [9,10].…”