Evaluation of imatinib mesylate as a possible treatment for nephrogenic systemic fibrosis in a rat model.

Abstract

INTRODUCTION:

The purpose of the study was to evaluate the efficacy of imatinib mesylate in the treatment of nephrogenic systemic fibrosis (NSF) in a rat model administered high-dose gadodiamide, erythropoietin (Epo) and intravenous iron (IV iron).

MATERIALS AND METHODS:

The local committee for animal research approved this study. Four groups of six Hannover-Wistar rats were studied. Group A received normal saline; Group B, IV iron and Epo; Group C, gadodiamide, IV iron and Epo; and Group D, gadodiamide, IV iron, Epo and imatinib. Gadodiamide was administered at 10 mmol/kg of body weight for 5 consecutive days. Imatinib was administered at 50 mg/kg starting 3 days before gadodiamide injections and was continued for 50 days afterwards. Biopsies were taken 3 and 7 weeks after gadodiamide injection, and dermal histology was analyzed as well as gadolinium deposition as measured by inductively coupled plasma mass spectrometry. Additionally, rats treated with gadodiamide were observed for a total of 16 weeks. For comparison of cellularity, a linear mixed-effects model was used, and for metal deposition, an analysis of variance was used, which was corrected with a Tamhane correction for unequal variances.

RESULTS:

Rats treated with gadodiamide in addition to IV iron and Epo (group C) had worse skin lesions on histology (P<.001) compared to control animals (groups A and B). Treatment with imatinib resulted in decreased cellularity (group D vs C, P<.001), although there was no difference in the amount of deposited gadolinium (P>.5). Histology at 16 weeks demonstrated increased fibrosis and dermal calcifications, consistent with the clinical presentation of NSF.

CONCLUSIONS:

The administration of imatinib to rats treated with high-dose gadodiamide resulted in decreased lesion severity.

• Authors: Thomas A Hope, Philip E Leboit, Whitney A High, Yanjun Fu, Robert C Brasch
• Journal: Magnetic resonance imaging (Magn Reson Imaging) Vol. 31 Issue 1 Pg. 139-44 (Jan 2013) ISSN: 1873-5894 [Electronic] Netherlands
• PMID: 22898683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Benzamides
• Contrast Media
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• gadodiamide
• Imatinib Mesylate
• Gadolinium DTPA

Topics

• Animals
• Benzamides (therapeutic use)
• Contrast Media (adverse effects)
• Gadolinium DTPA (adverse effects)
• Imatinib Mesylate
• Male
• Nephrogenic Fibrosing Dermopathy (drug therapy, pathology)
• Piperazines (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Pyrimidines (therapeutic use)
• Rats
• Rats, Wistar
• Treatment Outcome