*2.5.3 Impaired cardiac contraction*

The heart cells (cardiomyocytes) composed of myofibrils with typical contraction and relaxation. Pump and propel the blood to systemic circulation. Myofibrils contain multiple contractile units called sarcomere, which have actin and myosin filaments. In a calm state, actin is coated in tropomyosin and protects the myosin-binding sites. The troponin and tropomyosin are attached when the calcium enters into the cytosol from the sarcoplasmic reticulum; calcium binds to the troponin and the position of the tropomyosin and troponin changes resulting in shortening of the sarcomere. That specific condition termed as cardiac contraction controlled by calcium influx and myofilaments. DOX could affect the transcription and expression of the specific proteins [71]. Transcription factor-like GATA4 for the regulation of sarcomeric synthesis and cardiac differentiation and survival of myocytes. DOX-induced ROS decreases binding function, disrupts sarcomere structure, contractile reduction and myofibrillar deterioration [72]. DOX is believed to interact with calcium homeostasis by modifying the ion pump and modifying the ion channel movement, resulting in lipid peroxidation. ROS quickly targets the fatty acids of the membrane lipids and disrupts the mitochondrial calcium channels by increasing the activity of the voltage-sensitive L-type calcium channels on the cell membrane resulting in accumulation of calcium [73]. Calcium overload throughout cytosol, Causes the disruption in the contraction and relaxing of cardiomyocytes.
