ArticleScientific reports2016
Normal tissue radioprotection by amifostine via Warburg-type effects.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes.The Indian journal of medical research · 2025Review
- Preventive effects of melatonin and amifostine on irradiated rats with experimental periodontitis.BMC oral health · 2024Article
- Article
- Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.Frontiers in cell and developmental biology · 2024Review
- Human Intestinal Organoids and Microphysiological Systems for Modeling Radiotoxicity and Assessing Radioprotective Agents.Cancers · 2023Review
- An Adaptive Role for DNA Double-Strand Breaks in Hippocampus-Dependent Learning and Memory.International journal of molecular sciences · 2022Review
- Article
- Mitochondrial Superoxide Dismutase in Cisplatin-Induced Kidney Injury.Antioxidants (Basel, Switzerland) · 2021Review
- Three-Dimensional Cell Metabolomics Deciphers the Anti-Angiogenic Properties of the Radioprotectant Amifostine.Cancers · 2021Article
- Radioprotective Effects of Kelulut Honey in Zebrafish Model.Molecules (Basel, Switzerland) · 2021Article
- Cyclophosphamide-Induced Inflammation of Taste Buds and Cytoprotection by Amifostine.Chemical senses · 2021Article
- Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.Frontiers in oncology · 2021Review
- Radioprotection and Radiomitigation: From the Bench to Clinical Practice.Biomedicines · 2020Review
- Alterations in Tissue Metabolite Profiles with Amifostine-Prophylaxed Mice Exposed to Gamma Radiation.Metabolites · 2020Article
- Metabolic Pathways of the Warburg Effect in Health and Disease: Perspectives of Choice, Chain or Chance.International journal of molecular sciences · 2017Review
- Protective Effects of Polydatin on Reproductive Injury Induced by Ionizing Radiation.Dose-response : a publication of International Hormesis SocietyArticle
- RNA Profiling Reveals a Common Mechanism of Histone Gene Downregulation and Complementary Effects for Radioprotectants in Response to Ionizing Radiation.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.