The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues
by
Shashank Shrishrimal 1, Elizabeth A. Kosmacek 1, Arpita Chatterjee 1, McDonald J. Tyson 2
and Rebecca E. Oberley-Deegan 1,*
Shashank Shrishrimal 1, Elizabeth A. Kosmacek 1, Arpita Chatterjee 1, McDonald J. Tyson 2 and Rebecca E. Oberley-Deegan 1,*
1
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Department of Physics & Cancer Research Center, Hampton University, Hampton, VA 23668, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2017, 6(4), 87; https://doi.org/10.3390/antiox6040087
Received: 29 September 2017 / Revised: 25 October 2017 / Accepted: 31 October 2017 / Published: 6 November 2017
(This article belongs to the Special Issue Superoxide Dismutase (SOD) Enzymes, Mimetics and Oxygen Radicals)
Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure. Specifically, at two months post-radiation, MnTE-2-PyP inhibited the number of α-smooth muscle actin positive fibroblasts induced by radiation and at six months post-radiation, MnTE-2-PyP significantly reduced collagen deposition (fibrosis) in the skin and bladder tissues of irradiated mice. Radiation also resulted in changes to T cells. At two months post-radiation, there was a reduction of Th1-producing splenocytes, which resulted in reduced Th1:Th2 ratios. MnTE-2-PyP maintained Th1:Th2 ratios similar to unirradiated mice. At six months post-radiation, increased T cells were observed in the adipose tissues. MnTE-2-PyP treatment inhibited this increase. Thus, MnTE-2-PyP treatment maintains normal fibroblast function and T cell immunity months after radiation exposure. We believe that one of the reasons MnTE-2-PyP is a potent radioprotector is due to its protection of multiple cell types from radiation damage.
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Keywords:
MnTE-2-PyP; fibrosis; radiation; fibroblast; T cells; adipose; skin; bladder; NQO1; COL3A1
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MDPI and ACS Style
Shrishrimal, S.; Kosmacek, E.A.; Chatterjee, A.; Tyson, M.J.; Oberley-Deegan, R.E. The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues. Antioxidants 2017, 6, 87.
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