Assessment of cellular and molecular changes in the rat brain after gamma radiation and radioprotection by anisomycin

J Radiat Res. 2021 Sep 13;62(5):793-803. doi: 10.1093/jrr/rrab045.

Abstract

The objective of the study was to describe cellular and molecular markers of radioprotection by anisomycin, focusing on the changes in rat brain tissue. Two-month-old Wistar rats were exposed to a 60Co radiation source at a dose of 6 Gy, with or without radioprotection with anisomycin (150 mg/kg) administered subcutaneously 30 min before or 3 or 6 h after irradiation. Survivors were analyzed 30 days after treatment. Astroglial and microglial responses were investigated based on the expression of glial markers assessed with immunohistochemistry, and quantitative changes in brain biomolecules were investigated by Raman microspectroscopy. In addition, blood plasma levels of pro-inflammatory (interleukin 6 and tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines were assessed. We found that application of anisomycin either before or after irradiation significantly decreased the expression of the microglial marker Iba-1. We also found an increased intensity of Raman spectral bands related to nucleic acids, as well as an increased level of cytokines when anisomycin was applied after irradiation. This suggests that the radioprotective effects of anisomycin are by decreasing Iba-1 expression and stabilizing genetic material by increasing the level of nucleic acids.

Keywords: Raman microspectroscopy; anisomycin; cytokines; gamma radiation; glial cells; radioprotectors.

MeSH terms

  • Animals
  • Anisomycin / pharmacology
  • Anisomycin / therapeutic use*
  • Astrocytes / drug effects
  • Astrocytes / radiation effects
  • Brain / drug effects
  • Brain / radiation effects*
  • Calcium-Binding Proteins / biosynthesis
  • Calcium-Binding Proteins / genetics
  • Cobalt Radioisotopes
  • Cranial Irradiation / adverse effects*
  • Cytokines / blood
  • Gamma Rays / adverse effects*
  • Microfilament Proteins / biosynthesis
  • Microfilament Proteins / genetics
  • Microglia / drug effects
  • Microglia / radiation effects
  • Nucleic Acids / metabolism
  • Premedication
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / metabolism*
  • Radiation Injuries, Experimental / prevention & control
  • Radiation-Protective Agents / pharmacology
  • Radiation-Protective Agents / therapeutic use*
  • Rats
  • Rats, Wistar

Substances

  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Cobalt Radioisotopes
  • Cytokines
  • Microfilament Proteins
  • Nucleic Acids
  • Radiation-Protective Agents
  • Cobalt-60
  • Anisomycin