Evaluation of imatinib mesylate as a possible treatment for nephrogenic systemic fibrosis in a rat model
| Autor: | Robert C. Brasch, Thomas A. Hope, Yanjun Fu, Philip E. LeBoit, Whitney A. High |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Gadolinium DTPA
Male medicine.medical_specialty medicine.medical_treatment Gadolinium Biomedical Engineering Biophysics Urology Contrast Media chemistry.chemical_element Pharmacology Piperazines Nephrogenic Fibrosing Dermopathy Lesion medicine Animals Radiology Nuclear Medicine and imaging Rats Wistar Protein Kinase Inhibitors Saline business.industry Gadodiamide Imatinib medicine.disease Rats Pyrimidines Treatment Outcome Imatinib mesylate chemistry Erythropoietin Nephrogenic systemic fibrosis Benzamides Imatinib Mesylate medicine.symptom business medicine.drug |
| Zdroj: | Magnetic Resonance Imaging. 31:139-144 |
| ISSN: | 0730-725X |
| DOI: | 10.1016/j.mri.2012.06.027 |
| Popis: | 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).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.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.The administration of imatinib to rats treated with high-dose gadodiamide resulted in decreased lesion severity. |
| Databáze: | OpenAIRE |
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