Doxorubicin-induced Toxicity Through the p38 MAPK Protein Kinase Pathway

While exhibiting great value in treating multiple cancers, the chemotherapy drug, Doxorubicin, also manifests many side effects that significantly affect the post-chemotherapy life of patients. In the cardiac system, Doxorubicin causes oxidative stress due to increasing amount of Reactive oxygen species (ROS), and it promotes production of inflammatory cytokines. Oxidative stress and inflammatory cytokines then activate p38 mitogen-activated protein kinase (p38 MAPK), which can stimulate cardiomyocyte apoptosis. In the nervous system, Doxorubicin activates both extracellular signal-regulated kinase (ERK) and p38 MAPK. p38 MAPK predominately determines the result, leading to an overall reduction in Long-term Potentiation (LTP), or an analogous process of Long-term Facilitation (LTF). Moreover, neuroinflammatory effect achieved through the p38 MAPK pathway contributes to memory deficits by killing neurons excessively. Various inhibitors of p38 MAPK have shown promising results in lessening the effects of p38 MAPK, indicating future possibilities of using those inhibitors to ensure a safer application of Doxorubicin, while preserving the pharmacological values and properties of Doxorubicin.