Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice

J Biochem Mol Toxicol. 2020 Jun;34(6):e22479. doi: 10.1002/jbt.22479. Epub 2020 Mar 3.

Abstract

Purpose: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice.

Materials and methods: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant.

Results: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group.

Conclusions: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

Keywords: biochemical assays; biodistribution; montelukast; radioprotective; radiotherapy.

MeSH terms

  • Acetates / administration & dosage*
  • Animals
  • Antioxidants / administration & dosage*
  • Creatinine / blood
  • Creatinine / urine
  • Cyclopropanes / administration & dosage*
  • Gamma Rays / adverse effects*
  • Glutathione / analysis
  • Glutathione / metabolism
  • Kidney / metabolism
  • Leukotriene Antagonists / administration & dosage*
  • Male
  • Malondialdehyde / analysis
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Quinolines / administration & dosage*
  • Radiation-Protective Agents / administration & dosage*
  • Radiotherapy / adverse effects
  • Receptors, Leukotriene
  • Renal Insufficiency / blood
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / etiology*
  • Renal Insufficiency / urine
  • Sulfides / administration & dosage*

Substances

  • Acetates
  • Antioxidants
  • Cyclopropanes
  • Leukotriene Antagonists
  • Quinolines
  • Radiation-Protective Agents
  • Receptors, Leukotriene
  • Sulfides
  • Malondialdehyde
  • Creatinine
  • Glutathione
  • leukotriene D4 receptor
  • montelukast