Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis

Amitriptyline attenuates interstitial inflammation and ameliorates the progression of renal fibrosis

Author Achar, Eduardo Autor UNIFESP Google Scholar
Maciel, Thiago T. Autor UNIFESP Google Scholar
Collares, Carlos F. Google Scholar
Teixeira, Vicente de Paulo Castro Autor UNIFESP Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
São Paulo City Univ UNICID
São Paulo Poison Control Ctr
Abstract 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-beta 1 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.
Keywords amitriptyline
tubulointerstitial fibrosis
unilateral ureteral obstruction
Language English
Date 2009-03-01
Published in Kidney International. New York: Nature Publishing Group, v. 75, n. 6, p. 596-604, 2009.
ISSN 0085-2538 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 596-604
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000263723200007

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