Michael I Koukourakis1, Alexandra Giatromanolaki2, Konstantina Fylaktakidou3, Maria Kouroupi2, Efthimios Sivridis2, Christos E Zois4, Dimitra Kalamida5, Achilleas Mitrakas5, Stamatia Pouliliou5, Ilias V Karagounis5, Konstantinos Simopoulos6, David J P Ferguson4, Adrian L Harris4. 1. Department of Radiotherapy/Oncology, Democritus University of Thrace/University General Hospital of Alexandroupolis, Alexandroupolis, Greece targ@her.forthnet.gr. 2. Department of Pathology, Democritus University of Thrace/University General Hospital of Alexandroupolis, Alexandroupolis, Greece. 3. Department of Molecular Biology and Genetics, Democritus University of Thrace/University General Hospital of Alexandroupolis, Alexandroupolis, Greece. 4. CR UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, U.K. 5. Department of Radiotherapy/Oncology, Democritus University of Thrace/University General Hospital of Alexandroupolis, Alexandroupolis, Greece. 6. Department of Experimental Surgery, Democritus University of Thrace/University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND METHODS: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. RESULTS: 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. CONCLUSION: 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. Copyright
BACKGROUND/AIM: 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. MATERIALS AND METHODS: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. RESULTS: 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. CONCLUSION: 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. Copyright
Authors: Christos E Zois; Anne M Hendriks; Syed Haider; Elisabete Pires; Esther Bridges; Dimitra Kalamida; Dimitrios Voukantsis; B Christoffer Lagerholm; Rudolf S N Fehrmann; Wilfred F A den Dunnen; Andrei I Tarasov; Otto Baba; John Morris; Francesca M Buffa; James S O McCullagh; Mathilde Jalving; Adrian L Harris Journal: Cell Death Dis Date: 2022-06-28 Impact factor: 9.685
Authors: Michael I Koukourakis; Alexandra Giatromanolaki; Konstantina Fylaktakidou; Efthimios Sivridis; Christos E Zois; Dimitra Kalamida; Achilleas Mitrakas; Stamatia Pouliliou; Ilias V Karagounis; Konstantinos Simopoulos; David J P Ferguson; Adrian L Harris Journal: Invest New Drugs Date: 2018-01-31 Impact factor: 3.850