Amifostine Protects Mouse Liver Against Radiation-induced Autophagy Blockage.

Abstract

Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. The study provides evidence that ionizing radiation blocks autophagy activity and lysosomal biogenesis in normal mouse liver. Amifostine, protects the liver autophagic machinery and induces lysosomal biogenesis. By suppressing autophagy, ionizing radiation induces lipid droplet accumulation, while pre-treatment with amifostine protects lipophagy and up-regulates the TIP47 protein and mRNA levels, showing a maintenance of lipid metabolism in the liver cells. It is concluded that amifostine, aside to DNA protection activity, exerts its cytoprotective function by preventing radiation-induced blockage of autophagy, lysosomal biogenesis and lipophagy.