Abstract
Manganese superoxide dismutase (MnSOD) is a dominant component of the antioxidant defense system in mammalian cells. Since ionizing irradiation induces profound oxidative stress, it was logical to test the effect of overexpression of MnSOD on radioresistance. This task was accomplished by introduction of a transgene for MnSOD into cells in vitro and into organs in vivo, and both paradigms showed clear radioresistance following overexpression. During the course of development and clinical application of using MnSOD as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly which include (1) mitochondrial localization of either manganese superoxide dismutase or copper/zinc SOD was required to provide optimal radiation protection; (2) the time required for optimal expression was 12–18 h, and while acceptable for radiation protection, the time delay was impractical for radiation mitigation; (3) significant increases in intracellular elevation of MnSOD activity were required for effective radioprotection. Lessons learned during the development of MnSOD gene therapy have provided a strategy for delivery of small molecule SOD mimics, which are faster acting and have shown the potential for both radiation protection and mitigation. The purpose of this review is to summarize the current status of using MnSOD-PL and SOD mimetics as radioprotectors and radiomitigators.
Highlights
Manganese superoxide dismutase (MnSOD2 or SOD2) is a mitochondrial targeted antioxidant whose main responsibility is the dismutation of superoxides produced in the mitochondria during respiration [1,2,3]
Increased antioxidant activity provided by the overexpression of Manganese Superoxide Dismutase (MnSOD) in the mitochondria will aid in the preservation of the mitochondria to allow for the increased need of energy in the cell for repair of irradiation damage [1,2,3]
MnSOD-PL was effective in patients, as well as, in the mouse model and significantly reduced the objective and subjective parameters of esophagitis, most quantitated was the number of apoptotic cells per high power fields in standard histopathologic specimens
Summary
Manganese superoxide dismutase (MnSOD2 or SOD2) is a mitochondrial targeted antioxidant whose main responsibility is the dismutation of superoxides produced in the mitochondria during respiration [1,2,3]. The principles of clinical radiotherapy rely upon attention to detail regarding the physical parameters associated with an effective therapeutic ratio, including (1) minimizing the volume of normal tissue irradiated; (2) not exceeding the necessary therapeutic dose delivered; (3) the fraction size (dose given per day over a multiday/multiweek course of radiotherapy); (4) the overall duration (time course in days to weeks) of each particular treatment program. Another consideration is the history of Antioxidants 2021, 10, 1057.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
