Doxorubicin plus lonidamine: in vivo metabolic effects on the rat heart.

Lonidamine (LND) is a new drug that interferes with mitochondrial functions, thereby inhibiting cellular oxygen consumption and energy metabolism in both normal and neoplastic cells. These metabolic actions of LND seem to increase the cytotoxic effect of antitumor agents such as doxorubicin (Dx). Dx is a widely used antitumor agent, but the specific cardiac toxicity which develops at a critical cumulative dose is the major limiting factor in its long term use.

Anthracycline cardiotoxicity: in vivo and in vitro effects on biochemical parameters and heart ultrastructure of the rat.

The premise of this study is that mitochondrial lesions caused by anthracyclines lead directly to cardiotoxicity. We compared several biochemical parameters, including endogenous cellular respiration, adenosine and guanosine triphosphate levels, and 14C-amino acid incorporation, of rat hearts treated with doxorubicin and some of its derivatives, recent products of pharmacological research aimed at selecting less toxic antiblastic agents. In rats treated in vivo, we further examined the ultrastructural changes induced by anthracycline antibiotics in order to elucidate which biochemical parameters were consistent with the morphological lesions.

Doxorubicin and epirubicin cardiotoxicity: experimental and clinical aspects.

Epirubicin (EpiDx) belongs to the class of anthracycline antibiotics. It is an analog of doxorubicin (Dx) modified in the sugar moiety and in which the stereochemistry at the hydroxyl group bearing C-4' has been inverted. The purpose of this study was to evaluate in an experimental model and in a clinical trial the cardiotoxic effects of EpiDx vs Dx.

Protective effect of L-carnitine on cardiac metabolic damage induced by doxorubicin in vitro.

Carnitine, a naturally occurring compound which is an important cofactor in the transport of fatty acids within inner mitochondria, aids myocardial cells in efficiently meeting energy requirements. L-Carnitine has been texted in this study as a possible protective agent against doxorubicin-induced cardiac toxicity. Rat heart slices were incubated with doxorubicin (14 micrograms/ml), L-carnitine (600 micrograms/ml), and L-carnitine plus doxorubicin for 60 min at 38 degrees C.

Reduction of oxygen uptake in vitro as an index of cardiac toxicity induced by new anthracyclines.

Impairment of respiratory control in myocardial cells has been implicated in attempts to explain the cardiac toxicity of anthracycline antibiotics. This parameter has been found to correlate significantly with depletion of ATP and increase of Ca2+ intracellular concentration in rat heart slices. It has been suggested that 4'-deoxydoxorubicin and 4-demethoxydaunorubicin, whose molecular structures differ slightly from those of doxorubicin and daunorubicin, respectively, might be less cardiotoxic.