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.