**2.6 Diagnosis**

*Advances in Precision Medicine Oncology*

*2.5.4 Cell death*

myocytes [75].

*2.5.5 Autophagy*

subsequently lead to apoptosis of cell [77, 78].

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.

The general apoptosis is a process where a cell commits to suicide, damage to genetic material, protein, cellular organelles that beyond the repair would trigger the suicide to save the energy and resources. Apoptosis firmly regulated process involves intrinsic mitochondrial apoptosis, extrinsic death receptor pathways [74]. The mitochondrial pathway relays on the Trans membrane potential is a key indicator of membrane permeability. It is assumed that permeability can be either permeability-dependent or independent of the pore transition [PT]. The PT pore consists of the adenine nucleotide translocator, matrix protein cyclophilin D, and voltage-dependent anion channel. The opening of the PT pore activates the dissipation of the proton gradient produced by electron transport, resulting in the uncoupling of oxidative phosphorylation. The opening of the PT pore also allows water to penetrate the mitochondrial matrix, resulting in the swelling of the intermembrane space and the rupturing of the outer membrane allowing the release of apoptogenic proteins. Released proteins include cytochrome c, apoptosis-inducing factor and endonuclease G. Cytochrome c in conjunction with apoptosis protease activating factor (APAF-1) and pro-caspase 9 forms an apoptosome, which in turn activates effector caspases that collectively facilitate the execution of apoptosis. Due to decrease in the number of normal cardiomyocytes is significantly reduced, the heart failed to pump the blood sequentially ventricular remodelling and death of

The death receptor pathway involves the binding of death ligands such as FasL, TNF-α to their respective membrane-bound receptors. The bonded ligands signals to various proteins mediate the cascade, which leads to apoptosis of the cell [76]. In cancer therapy, DOX-induced ROS activates the p38, p53 and NF-kB pathways resulting in the differences in pro- and anti-apaptonic signalling imbalance, such imbalance cause release of cytochrome C from mitochondrial membrane proteins,

Autophagy is a method of restoring or repairing the destroyed cells. It is a self-degrading mechanism (survival mechanism) to maintain a balance of life in response to dietary stress, energy depletion. Autophagy destroys malformed proteins, weakened organelles, and other cell infections, which can be unique or non-specific, but processes are not completely thought out. Under diseased

**176**

The DOX-induced cardiomyopathy consists of a complete examination of the cardiovascular system for detecting the symptoms, such as S3 gallop and elevated jugular vapour pressure, T wave impairments; low voltage QRS complexes are measured.

