Optimal conditions of LDR to protect the kidney from diabetes: exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes

Life Sci. 2014 May 8;103(1):49-58. doi: 10.1016/j.lfs.2014.02.037. Epub 2014 Mar 11.

Abstract

Aims: We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes.

Main methods: Male C57BL/6J mice with type 1 diabetes were induced with multiple injections of low-dose streptozotocin. Diabetic mice received whole body X-irradiation at a dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th weeks of the study.

Key findings: Diabetes induced renal dysfunction is shown by the decreased creatinine and increased microalbumin in the urine. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best protective effect on the kidney of diabetic mice.

Significance: Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes.

Keywords: Diabetic nephropathy; Low-dose radiation; Radiation adaptive response; Radiation hormesis; Renal pathogenesis; Renal remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Dose-Response Relationship, Radiation
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney / radiation effects
  • Lipid Peroxidation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Radiotherapy / methods*
  • Whole-Body Irradiation

Substances

  • Blood Glucose