Effect of adriamycin on lipid peroxide, glutathione peroxidase and respiratory responses of mitochondria from the heart, liver and kidney.

Doxorubicin‐Induced Cardiotoxicity: From Bioenergetic Failure and Cell Death to Cardiomyopathy

“…DOX also coordinates with free transitional metals, such as iron, to form metal coordination complexes and stimulate production of partially reduced forms of oxygen . DOX‐induced oxygen‐free radicals can damage phospholipids in biological membranes, increasing the cell membrane permeability and inactivating membrane receptors and other enzymes . DOX also presents a strong affinity for cardiolipin, one of the most abundant phospholipids in the inner mitochondrial membrane (IMM) and which is required for the activity of respiratory chain enzymes such as cytochrome c oxidase and NADH cytochrome c oxidoreductase .…”

Assay for flavins in rat heart mitochondria by high pressure liquid chromatography.

“…The biochemical properties of mitochondria prepared from rat heart by our pres-ent procedure have been described in a separate paper (Yoon et al 1983, Kagiyama, 1985. Typical values obtained from a polarographic assay of mitochondrial respiratory responses are shown in Table 2.…”

Mitochondria as a Biosensor for Drug-induced Toxicity – Is It Really Relevant?

“…The onset of DOX-induced cardiomyopathy is characterized by several forms of tachycardia (Bristow, Minobe et al, 1981), altered left ventricular function (Hrdina, Gersl et al, 2000), and severe histological changes such as vacuolization of the cytoplasm, loss of myofibrils, altered sarcoplasmic reticulum, deposition of lipid droplets, and mitochondrial swelling (Lefrak, Pitha et al, 1973;Olson & Capen, 1978;Iwasaki & Suzuki, 1991;Sardao, Oliveira et al, 2009). More evidence suggests that mitochondria are a critical target in the development of DOX-induced cardiomyopathy (Yoon, Kajiyama et al, 1983;Praet & Ruysschaert, 1993;Jung & Reszka, 2001;Wallace, 2003;. Numerous mechanisms for the toxicity of DOX on cardiac mitochondrial function have been proposed, such as generation of free radicals (Muraoka & Miura, 2003), interaction with mitochondrial DNA (L'Ecuyer, Sanjeev et al, 2006), disruption of cardiac gene expression , alteration of calcium homeostasis (Lebrecht, Kirschner et al), lipid peroxidation mediating disturbance of mitochondrial membranes (Mimnaugh, Trush et al, 1985), and inhibition of mitochondrial respiration chain, decreasing both intracellular ATP and phosphocreatine (PCr) (TokarskaSchlattner, Zaugg et al, 2006).…”