Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse KidneyScharpfenecker, M., Floot, B., Russell, N. S., Coppes, R. P. & Stewart, F. A., 1-Jul-2014, In : International Journal of Radiation Oncology Biology Physics. 89, 3, p. 599-606 8 p.
Research output: Contribution to journal › Article › Academic › peer-review
Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney.
Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation.
Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function.
Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function. (C) 2014 Elsevier Inc.
|Number of pages||8|
|Journal||International Journal of Radiation Oncology Biology Physics|
|Publication status||Published - 1-Jul-2014|
- IONIZING-RADIATION, FIBROSIS, MICE, ANGIOGENESIS, PERICYTES, RADIOBIOLOGY, PERSPECTIVES, PROGRESSION, PREVENTS, CELLS