管理多克索鲁比心脏毒性:洞察分子机制和保护策略

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...

Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...