The effect of selected drugs on the mitigation of myocardial injury caused by gamma radiation

Can J Physiol Pharmacol. 2021 Jan;99(1):80-88. doi: 10.1139/cjpp-2020-0323. Epub 2021 Jan 13.

Abstract

Radiation damage of healthy tissues represents one of the complications of radiotherapy effectiveness. This study is focused on the screening of potentially effective drugs routinely used in medical practice and involved in the mechanism of radiation injury, namely for radiation-induced production of free radicals in the body. Experiments in rats revealed significant reduction of oxidative stress (malondialdehyde) and inflammatory marker (tumor necrosis factor α) in 10 Gy irradiated groups after administration of atorvastatin and a slight decrease after tadalafil administration, which indicates that one of the possible mechanisms for mitigation of radiation-induced cardiac damage could be the modulation of nitric oxide (NO) in endothelium and phosphodiesterase 5. In addition, miRNAs were analyzed as potential markers and therapeutically effective molecules. Expression of miRNA-21 and miRNA-15b showed the most significant changes after irradiation. Atorvastatin and tadalafil normalized changes of miRNA (miRNA-1, miRNA-15b, miRNA-21) expression levels in irradiated hearts. This screening study concludes that administration of specific drugs could mitigate the negative impact of radiation on the heart, but more detailed experiments oriented to other aspects of drug effectiveness and their exact mechanisms are still needed.

Keywords: acetylsalicylic acid; acide acétylsalicylique; atorvastatin; atorvastatine; inflammation; miARN; miRNAs; myocarde; myocardium; oxidative stress; radiation; rayonnements; sildenafil; sildénafil; stress oxydatif; tadalafil.

MeSH terms

  • Animals
  • Atorvastatin / administration & dosage*
  • Cardiomyopathies / blood
  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / etiology
  • Free Radicals / blood
  • Free Radicals / metabolism
  • Gamma Rays / adverse effects
  • Heart / drug effects*
  • Heart / radiation effects
  • Male
  • Malondialdehyde / blood
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Radiation Injuries, Experimental / blood
  • Radiation Injuries, Experimental / diagnosis
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / etiology
  • Rats
  • Tadalafil / administration & dosage*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Free Radicals
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Tadalafil
  • Atorvastatin