Multiple mechanisms of cardiotoxicity induced by DOX
| Mechanism | Reference |
|---|---|
| Lipid peroxidation | Li and Singal, 2000 |
| Pacher et al., 2003 | |
| Inhibition of nucleic acids and protein synthesis; release of vasoactive amines | Olson and Mushlin, 1990 |
| Changes in adrenergic function and adenylate cyclase | Kalyanaraman et al., 2002 |
| Singal and Iliskovic, 1998 | |
| Singal et al., 2000 | |
| Inhibition of spontaneous or caffeine-induced sarcoplasmic reticulum Ca2+ release | Olson et al., 2000 |
| Shadle et al., 2000. | |
| Reduced expression of: | Arai et al., 1998 |
| Gambliel et al., 2002 | |
| α-Actin, myosin light chain 2 slow, troponin I | Ito et al., 1990 |
| SR Ca2+ -ATPase and Ca2+ -gated Ca2+ release channel (RyR-2) | Jeyaseelan et al., 1997a |
| Phospholamban, calsequestrin | Jeyaseelan et al., 1997b |
| Rieske iron-sulfur protein | Torti et al., 1998 |
| ADP/ATP translocase, phosphofructokinase, Mt-CK | Zhou et al., 2001b. |
| Irreversible decrease in mitochondrial Ca2+ loading and ATP content | Zhou et al., 2001a |
| Impairment of membrane binding, assembly, and activity of MtCK | Tokarska-Schlattner et al., 2002 |
| Peroxynitrite-dependent nitration/inactivation of Mt-CK or nitration/activation of metalloproteinases | Mihm et al., 2002 |
| Pacher et al., 2003 | |
| Weinstein et al., 2000 |
M-CK, myofibrillar creatine kinase; Mt-CK, mitochondrial creatine kinase; RyR-2, ryanodine receptor 2; SR, sarcoplasmic reticulum.