Abstract
Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown “mito-protective” properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study.
Keywords: Salen manganese complex, radiation injury, radiation mitigation, catalytic antioxidant, ionizing radiation, EUK-207, astrocyte cultures, radiation therapy, oxidative stress, proinflammatory processes, radiation countermeasures area, cytotoxicity, catalase activity
Anti-Cancer Agents in Medicinal Chemistry
Title: Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues
Volume: 11 Issue: 4
Author(s): Rosalind A. Rosenthal, Brian Fish, Richard P. Hill, Karl D. Huffman, Zelmira Lazarova, Javed Mahmood, Meetha Medhora, Robert Molthen, John E. Moulder, Stephen T. Sonis, Philip J. Tofilon and Susan R. Doctrow
Affiliation:
Keywords: Salen manganese complex, radiation injury, radiation mitigation, catalytic antioxidant, ionizing radiation, EUK-207, astrocyte cultures, radiation therapy, oxidative stress, proinflammatory processes, radiation countermeasures area, cytotoxicity, catalase activity
Abstract: Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown “mito-protective” properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study.
Export Options
About this article
Cite this article as:
A. Rosenthal Rosalind, Fish Brian, P. Hill Richard, D. Huffman Karl, Lazarova Zelmira, Mahmood Javed, Medhora Meetha, Molthen Robert, E. Moulder John, T. Sonis Stephen, J. Tofilon Philip and R. Doctrow Susan, Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (4) . https://dx.doi.org/10.2174/187152011795677490
DOI https://dx.doi.org/10.2174/187152011795677490 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Hydrophobic Modification of Copper Nanospheres for Incorporation into Poloxamer Micelles, Aggregated Micellar Nanocages and Supramolecular Assemblies
Current Nanomedicine The Protein-Protein Interaction-Mediated Inactivation of PTEN
Current Molecular Medicine Sp/KLF Family and Tumor Angiogenesis in Pancreatic Cancer
Current Pharmaceutical Design Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer
Current Medicinal Chemistry The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors
Mini-Reviews in Medicinal Chemistry Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research
Current Pharmaceutical Design Neuropilin Signalling in Vascular Development and Pathology
Current Angiogenesis (Discontinued) NUPR1 Interacts with p53, Transcriptionally Regulates p21 and Rescues Breast Epithelial Cells from Doxorubicin-Induced Genotoxic Stress
Current Cancer Drug Targets Delivery of Intracellular-Acting Biologics in Pro-Apoptotic Therapies
Current Pharmaceutical Design Stem Cells as In Vitro Models of Disease
Current Stem Cell Research & Therapy Prospective Function of Different Antioxidant Containing Natural Products in the Treatment of Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Strategies for Preparing Different Types of Lipid Polymer Hybrid Nanoparticles in Targeted Tumor Therapy
Current Pharmaceutical Design Topoisomerase I Inhibitors in the Treatment of Primary CNS Malignancies: An Update on Recent Trends
Anti-Cancer Agents in Medicinal Chemistry Establishment of Cholinergic Neuron-like Cell Lines with Differential Vulnerability to Nitrosative Stress
Current Neurovascular Research Prediction of the Ebola Virus Infection Related Human Genes Using Protein-Protein Interaction Network
Combinatorial Chemistry & High Throughput Screening The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology
Current Molecular Medicine Assessment of Gene Transfer Using Imaging Methodology
Current Genomics Cellular Iron Homeostasis and Therapeutic Implications of Iron Chelators in Cancer
Current Pharmaceutical Biotechnology Polymer Particulates in Drug Delivery
Current Pharmaceutical Design Beyond Oncolytic Virotherapy: Replication-Competent Retrovirus Vectors for Selective and Stable Transduction of Tumors
Current Gene Therapy