Table 2.

Summary of major pathways affected by cardiotoxic drugs within the different cardiac cell types.

Type of cell	Drug	Molecular pathway
Cardiac fibroblasts	Doxorubicin	(i) Activation of TGF-β and collagen deposition (ii) Activation of ATM (iii) Release of Fas-L and activation of apoptosis
	Cobalt	(i) Reduction of MnSOD and reduced ROS scavenger capacity
Endothelial cells	Doxorubicin	(i) Increase of cellular permeability (ii) Reduction of GSH, MnSOD, and reduced ROS scavenger capacity (iii) Reduction of ATP and mitochondrial dysfunction (iv) Inhibition of NO synthase (v) Activation of NFκB and release of IL-1/IL-2/IL-6
	Cyclophosphamide	(i) Increase of cellular permeability (ii) Activation of NFκB and release of IL-1/IL-2/IL-6
	Cisplatinum	(i) Reduction of GSH, MnSOD, and reduced ROS scavenger capacity (ii) Activation of NFκB and release of IL-1/IL-2/IL-6
	Trastuzumab	(i) Inhibition of NO synthase
	Sorafenib	(i) Activation of endothelin 1
Vascular smooth muscle cells	Doxorubicin	(i) Activation of senescence (ii) Downregulation of α-adrenoreceptor and reduction of contractility
Immune cells	Doxorubicin	(i) Activation of innate immune response (ii) Activation of NLRP3 inflammasome and release of IL-1β and MCP-1
	Trastuzumab	(i) Increase of NFκB expression (ii) Increase of NADPH subunit levels
	Sunitinib	(i) Increase of NFκB expression (ii) Increase of NADPH subunit levels
Cardiac progenitor cells	Doxorubicin	(i) Oxidative DNA damage and activation of ATM and p53 (ii) Increase of p16 INK4 and activation of senescence (iii) Reduction of IGF-1 and c-Met with reduction of survival and cell migration (iv) Reduction of MnSOD, Cu/Zn SOD, catalase, and reduced ROS scavenger capacity (v) Increase of apoptosis and inhibition of cardiac differentiation
	5-Fluorouracil	(i) Increase of apoptosis and inhibition of cardiac differentiation
	Trastuzumab	(i) Increase of apoptosis and inhibition of cardiac differentiation