Mitochondria has essential role in myocardial tissue homeostasis, thus deterioration
in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death
and consequent cardiovascular dysfunction. Several chemical compounds and drugs have
been known to modulate directly or indirectly cardiac mitochondrial function which
can account both for the toxicological and pharmacological properties of these substances.
In many cases toxicity problems appear only in the presence of additional cardiovascular
disease conditions or develop months/years following the exposure making the diagnosis
difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer
drugs (anthracyclines - (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin),
arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), and bevacizumab
(Avastin), sunitinib (Sutent) and sorafenib (Nevaxar)), antiviral compound azidothymidine
(AZT, Zidovudine) and several oral antidiabetics (e.g. rosiglitazone (Avandia)). Illicit
drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids
(spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity
develops due to various mechanisms, involving interference with the mitochondrial
respiratory chain (e.g. uncoupling), or due to inhibition of the important mitochondrial
enzymes (oxidative phosphorylation, Szent-Gyorgyi-Krebs cycle, mitochondrial DNA replication,
ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of
mitochondrial membrane potential, increase in mitochondrial oxidative/nitrative stress,
eventually culminating into cell death. This review aims to discuss the mechanisms
of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential
cardioprotective strategies to prevent these toxicities.
