Molecular Mechanisms of Renal Cellular Nephrotoxicity due to Radiocontrast Media

Figure 1

Scheme showing the effects of RCM on signaling molecules. The scheme relates to effects on signaling molecules that may underlie the toxic effects of RCM. RCM cause inactivation of the kinase Akt (as shown by the minus symbol) leading to activation of FoxO transcription factors which may lead to cell death; upregulation of ET-1 transcription and hence vasoconstriction; deactivation of the p70S6 kinase and hence downregulation of protein synthesis. ERK1/2 are also inactivated which may lead to a decrease in activity of COX-2 and prostaglandin production and hence inhibition of vasodilation. RCM also downregulate cAMP and hence the cAMP dependent kinase PKA. The antiapoptotic protein Bcl-2 is downregulated, whilst the proapoptotic proteins Bax, Bim, Bad, and caspases-3 and -9 are upregulated (as shown by the plus symbol) by RCM. The JNK and p38 MAP kinases are activated as also is the transcription factor NF-𝜅B, all three of which may play a role in cell death and inflammation. Hypoxia and mitochondrial damage caused by RCM may lead to the formation of ROS (reactive oxygen species) that can cause cell death and inflammation; and to the formation of adenosine that can cause vasoconstriction, whilst its metabolism by xanthine oxidase can lead to further formation of ROS.