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CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5.

Publication ,  Journal Article
Leu, D; Spasojevic, I; Nguyen, H; Deng, B; Tovmasyan, A; Weitner, T; Sampaio, RS; Batinic-Haberle, I; Huang, T-T
Published in: Redox Biol
August 2017

Although radiation therapy can be effective against cancer, potential damage to normal tissues limits the amount that can be safely administered. In central nervous system (CNS), radiation damage to normal tissues is presented, in part, as suppressed hippocampal neurogenesis and impaired cognitive functions. Mn porphyrin (MnP)-based redox active drugs have demonstrated differential effects on cancer and normal tissues in experimental animals that lead to protection of normal tissues and radio- and chemo-sensitization of cancers. To test the efficacy of MnPs in CNS radioprotection, we first examined the tissue levels of three different MnPs - MnTE-2-PyP5+(MnE), MnTnHex-2-PyP5+(MnHex), and MnTnBuOE-2-PyP5+(MnBuOE). Nanomolar concentrations of MnHex and MnBuOE were detected in various brain regions after daily subcutaneous administration, and MnBuOE was well tolerated at a daily dose of 3mg/kg. Administration of MnBuOE for one week before cranial irradiation and continued for one week afterwards supported production and long-term survival of newborn neurons in the hippocampal dentate gyrus. MnP-driven S-glutathionylation in cortex and hippocampus showed differential responses to MnP administration and radiation in these two brain regions. A better understanding of how preserved hippocampal neurogenesis correlates with cognitive functions following cranial irradiation will be helpful in designing better MnP-based radioprotection strategies.

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Published In

Redox Biol

DOI

EISSN

2213-2317

Publication Date

August 2017

Volume

12

Start / End Page

864 / 871

Location

Netherlands

Related Subject Headings

  • Radiation-Protective Agents
  • Oxidative Stress
  • Neurogenesis
  • Mice, Inbred C57BL
  • Metalloporphyrins
  • Male
  • Hippocampus
  • Female
  • Cranial Irradiation
  • Cerebral Cortex
 

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Leu, D., Spasojevic, I., Nguyen, H., Deng, B., Tovmasyan, A., Weitner, T., … Huang, T.-T. (2017). CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5. Redox Biol, 12, 864–871. https://doi.org/10.1016/j.redox.2017.04.027
Leu, David, Ivan Spasojevic, Huy Nguyen, Brian Deng, Artak Tovmasyan, Tin Weitner, Romulo S. Sampaio, Ines Batinic-Haberle, and Ting-Ting Huang. “CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5.Redox Biol 12 (August 2017): 864–71. https://doi.org/10.1016/j.redox.2017.04.027.
Leu, David, et al. “CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5.Redox Biol, vol. 12, Aug. 2017, pp. 864–71. Pubmed, doi:10.1016/j.redox.2017.04.027.
Leu D, Spasojevic I, Nguyen H, Deng B, Tovmasyan A, Weitner T, Sampaio RS, Batinic-Haberle I, Huang T-T. CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5. Redox Biol. 2017 Aug;12:864–871.
Journal cover image

Published In

Redox Biol

DOI

EISSN

2213-2317

Publication Date

August 2017

Volume

12

Start / End Page

864 / 871

Location

Netherlands

Related Subject Headings

  • Radiation-Protective Agents
  • Oxidative Stress
  • Neurogenesis
  • Mice, Inbred C57BL
  • Metalloporphyrins
  • Male
  • Hippocampus
  • Female
  • Cranial Irradiation
  • Cerebral Cortex