Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

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• 作者：Marion Scharpfenecker ; PhD^&lowast ; ; ^{m.scharpfenecker@nki.nl" class="auth_mail} ; Ben Floot^&lowast ; ; Nicola S. Russell ; MD ; PhD^&dagger ; ; Rob P. Coppes ; PhD^&Dagger ; ; Fiona A. Stewart ; PhD^&lowast ;
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：1 July 2014
• 年：2014
• 卷：89
• 期：3
• 页码：599-606
• 全文大小：2724 K

文摘

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.