Radioprotective effect of atorvastatin against ionizing radiation-induced nephrotoxicity in mice

Int J Radiat Biol. 2018 Feb;94(2):106-113. doi: 10.1080/09553002.2018.1420926. Epub 2018 Jan 8.

Abstract

Purpose: Kidneys are exposed to ionizing radiation during radiotherapy in patients with abdominal malignancy. The aim of this study is to investigate the protective effect of atorvastatin (ATV) against ionizing radiation-induced nephrotoxicity in mice.

Materials and methods: Sixty male BALB/c mice were randomly divided into six groups (10 mice per group); control, irradiation (IR), IR plus ATV (10, 20 and 50 mg/kg) and only ATV (50 mg/kg). ATV groups received ATV for seven days via oral gavage before exposure to IR. Animals were exposed to 2 Gy whole body of X-ray on day 8. After exposure to IR, biochemical, histological and immunohistological assays were performed.

Results: ATV significantly decreased the level of oxidative stress biomarkers in irradiated mice in comparison with IR alone. A significant reduction in the urea and creatinine levels was observed in ATV plus IR group compared to IR alone. Tubular degeneration, glomerular atrophy, interstitial expansion and fibrosis were observed in irradiated mice. Tubular degeneration and atrophy in the kidneys of IR plus ATV group were less than IR group. In addition, pre-treated animal with ATV significantly showed reduction in caspase-3 immunoreactivity.

Conclusion: ATV has significant protective effect against radiation-induced nephrotoxicity in mice and is a promising medication for protection of patients during radiotherapy.

Keywords: Ionizing radiation; atorvastatin; nephrotoxicity; oxidative stress; radioprotective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Atorvastatin / pharmacology*
  • Caspase 3 / metabolism
  • Creatinine / blood
  • Disease Models, Animal
  • Fibrosis
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Kidney / drug effects*
  • Kidney / radiation effects*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / radiation effects
  • Lipid Peroxidation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxidative Stress
  • Radiation Protection
  • Radiation, Ionizing
  • Radiation-Protective Agents / pharmacology*
  • Urea / blood
  • X-Rays

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Radiation-Protective Agents
  • Urea
  • Atorvastatin
  • Creatinine
  • Casp3 protein, mouse
  • Caspase 3