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This Article Full Text Full Text (PDF) All Versions of this Article: 297/6/E1366    most recent ajpendo.00478.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, C. Articles by Cai, L. PubMed PubMed Citation Articles by Zhang, C. Articles by Cai, L.

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

¹School of Public Health of Jilin University, Changchun, China; ²Department of Pediatrics, University of Louisville, Louisville, Kentucky; ³Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou; ⁴The First Hospital of Jilin University; ⁵School of Pharmacy of Jilin University, Changchun; ⁶Engineering 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 ⁷Departments 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 suggest that multiple exposures to LDR significantly suppress diabetes-induced systemic and renal inflammatory response and renal oxidative damage, resulting in a prevention of the renal dysfunction and fibrosis.

diabetic nephropathy; renal oxidative damage; inflammatory factors; radio-adaptive response; radiation hormesis