Can Dexmedetomidine Be Effective in the Protection of Radiotherapy-Induced Brain Damage in the Rat?

Neurotox Res. 2021 Aug;39(4):1338-1351. doi: 10.1007/s12640-021-00379-1. Epub 2021 May 31.

Abstract

Approximately 7 million people are reported to be undergoing radiotherapy (RT) at any one time in the world. However, it is still not possible to prevent damage to secondary organs that are off-target. This study, therefore, investigated the potential adverse effects of RT on the brain, using cognitive, histopathological, and biochemical methods, and the counteractive effect of the α2-adrenergic receptor agonist dexmedetomidine. Thirty-two male Sprague Dawley rats aged 5-6 months were randomly allocated into four groups: untreated control, and RT, RT + dexmedetomidine-100, and RT + dexmedetomidine-200-treated groups. The passive avoidance test was applied to all groups. The RT groups received total body X-ray irradiation as a single dose of 8 Gy. The rats were sacrificed 24 h after X-ray irradiation, and following the application of the passive avoidance test. The brain tissues were subjected to histological and biochemical evaluation. No statistically significant difference was found between the control and RT groups in terms of passive avoidance outcomes and 8-hydroxy-2'- deoxyguanosine (8-OHdG) positivity. In contrast, a significant increase in tissue MDA and GSH levels and positivity for TUNEL, TNF-α, and nNOS was observed between the control and the irradiation groups (p < 0.05). A significant decrease in these values was observed in the groups receiving dexmedetomidine. Compared with the control group, gradual elevation was determined in GSH levels in the RT group, followed by the RT + dexmedetomidine-100 and RT + dexmedetomidine-200 groups. Dexmedetomidine may be beneficial in countering the adverse effects of RT in the cerebral and hippocampal regions.

Keywords: Brain; Dexmedetomidine; Radiotherapy; Rat.

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / radiation effects
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Dexmedetomidine / pharmacology
  • Dexmedetomidine / therapeutic use*
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / prevention & control*
  • Radiotherapy / adverse effects
  • Radiotherapy / methods
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Neuroprotective Agents
  • Dexmedetomidine