Attenuation of diabetes-induced renal dysfunction by multiple exposures to low-dose radiation is associated with the suppression of systemic and renal inflammation

1 School of Public Health of Jilin University, Changchun, China; 2 Department of Pediatrics, University of Louisville, Louisville, Kentucky; 3 Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou; 4 The First Hospital of Jilin University; 5 School of Pharmacy of Jilin University, Changchun; 6 Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun, and Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, Wenzhou, China; and 7 Departments of Medicine and Radiation Oncology, University of Louisville, Louisville, Kentucky Submitted 3 August 2009 ; accepted in final form 27 September 2009 Renal protection against diabetes-induced pathogenic injuries by multiple exposures to low-dose radiation (LDR) was investigated to develop a novel approach to the prevention of renal disease for diabetic subjects. C57BL/6J mice were given multiple low-dose streptozotocin (STZ; 60 x 6 mg/kg) to produce a type 1 diabetes. Two weeks after diabetes onset, some of diabetic mice and age-matched nondiabetic mice were exposed whole body to 25 mGy X-rays every other day for 2, 4, 8, 12, and 16 wk. Diabetes caused a significant renal dysfunction, shown by time-dependent increase in urinary microalbumin (Malb) and decrease in urinary creatinine (Cre), and pathological changes, shown by significant increases in renal structural changes and PAS-positive staining. However, diabetes-induced renal dysfunction and pathological changes were significantly, albeit partially, attenuated by multiple exposures to LDR. Furthermore, LDR protection against diabetes-induced renal dysfunction and pathological changes was associated with a significant suppression of diabetes-increased systemic and renal inflammation, shown by significant increases in serum and renal TNF , ICAM-1, IL-18, MCP-1, and PAI-1 contents. To further explore the mechanism by which LDR prevents diabetes-induced renal pathological changes, renal oxidative damage was examined by Western blotting and immunohistochemical staining for 3-nitrotyrosine and 4-hydroxynonenal. Significant increase in oxidative damage was observed in diabetic mice, but not diabetic mice, with LDR. Renal fibrosis, examined by Western blotting of connective tissue growth factor and Masson's trichrome staining, was also evident in the kidneys of diabetic mice but not diabetic mice with LDR. These results s