Involvement of the Bufodienolides in Disorders of Inflammation, Body Volume, Tissue Injury, and Ischemia

Abstract

The bufodienolides are a group of circulating steroid hormones which, along with the cardenolides, compose the compounds referred to as the “cardiotonic steroids” or “cardiac glycosides.” The most extensively studied of the bufodienolides is marinobufogenin (MBG). Recent evidence indicates that at least some of the effects of MBG are mediated by alterations in the MAPK signaling cascade. Previous investigations have largely been directed towards the involvement of the bufodienolides in changes in body volume and hypertension, including volume expansion-mediated essential hypertension, as well as the pregnancy-specific hypertensive disorder, preeclampsia. However, it is now clear that MBG and its antagonist, resibufogenin (RBG), are implicated in disorders characterized by the generation and maintenance of inflammation. Therefore, evidence has been presented in this review which implicates MBG in traumatic brain injury and the acute respiratory distress syndrome. Furthermore, not only does RBG prevent preeclampsia in a rat model of the disturbance, but it is also effective in ameliorating the abnormalities in traumatic brain injury. Efforts are currently underway to determine if, as is the case in the latter two disorders, it is also effective in modifying the course of the disease in the acute respiratory distress syndrome. Thus, the investigative future seems bright with regard to the potential activity of these and other bufodienolides in medicine.