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598503 
Journal Article 
Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis 
Achar, E; Maciel, TT; Collares, CF; Teixeira, VPC; Schor, N 
2009 
1 
Kidney International
ISSN: 0085-2538
EISSN: 1523-1755 
75 
6 
596-604 
Amitriptyline is a pleiotropic tricyclic antidepressant, which has anti-oxidant and anti-inflammatory properties. We tested whether amitriptyline might be useful in the treatment of chronic renal disease using the mouse model of unilateral ureteral obstruction. Amitriptyline caused a significant reduction of interstitial fibrosis, determined by Masson's staining, with minimal myofibroblast formation and macrophage infiltration following ureteral obstruction. Using quantitative PCR we found that this treatment significantly reduced the expression of key molecular markers of progressive tubulointerstitial injury such as osteopontin, MCP-1, ICAM-1, and TGF-β1 compared to their level in a saline-treated control group. Sublethal X-irradiation or mycophenolate mofetil, treatments that reduce inflammation, were comparable to amitriptyline in the reduction of interstitial fibrosis and macrophage infiltration. These studies in animals suggest that amitriptyline is worth testing as a therapeutic agent that might preserve renal function by blocking inflammation and renal fibrosis.Kidney International (2009) 75, 596–604; doi:10.1038/ki.2008.578; published online 26 November 2008 [ABSTRACT FROM AUTHOR] Copyright of Kidney International is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts) 
CELL adhesion molecules; KIDNEYS -- Diseases; CHRONIC renal failure; MYOFIBROBLASTS; FIBROBLASTS; amitriptyline; inflammation; tubulointerstitial fibrosis; unilateral ureteral obstruction