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This Article 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 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.

RESEARCH ARTICLE

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

¹Jilin University ²University of Louisville

Submitted 3 August 2009 ; revised 21 September 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 in order 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 mg/kg x 6) to produce a type 1 diabetes. Two weeks after diabetes onset, some of diabetic mice and age-matched non-diabetic mice were exposed whole-body to 25 mGy X-rays every other day for 2, 4, 8, 12 and 16 weeks. 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, though 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.

Low dose radiation; Diabetic nephropathy; renal inflammation; renal oxidative damage; renal dysfunction