Document Detail


Apocynin attenuates tubular apoptosis and tubulointerstitial fibrosis in transgenic mice independent of hypertension.
MedLine Citation:
PMID:  18923387     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiotensin II stimulates the formation of reactive oxygen species by increased NADPH oxidase activity, which contributes to proapoptotic and profibrotic mechanisms critical in renal injury. Here we determine if apocynin, an inhibitor of NADPH oxidase, interferes with the action of the intrarenal renin-angiotensin system to minimize the progression of renal disease. Transgenic mice that overexpress rat angiotensinogen in their proximal tubule cells were given either apocynin, perindopril, or hydralazine while untreated or apocynin-treated non-transgenic littermates served as controls. Untreated transgenic mice had significant elevations of their systolic blood pressure, albuminuria, reactive oxygen species production, NADPH oxidase activity, tubular apoptosis, active caspase-3, Bax, transforming growth factor-beta1, plasminogen activator inhibitor-1, extracellular matrix proteins, collagen type IV, and phosphorylated p47phox expression compared to untreated non-transgenic mice. Apocynin and perindopril blunted these changes; however, apocynin had no effect on the systolic blood pressure whereas hydralazine prevented hypertension and tubulointerstitial fibrosis but not proximal tubule cell apoptosis. Our study shows that the intrarenal renin-angiotensin system stimulates proximal tubule cell apoptosis and tubulointerstitial fibrosis, in part, by enhanced NADPH oxidase activity and reactive oxygen species generation independent of systemic hypertension.
Authors:
Fang Liu; Chih-Chang Wei; Shyh-Jong Wu; Isabelle Chenier; Shao-Ling Zhang; Janos G Filep; Julie R Ingelfinger; John S D Chan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-15
Journal Detail:
Title:  Kidney international     Volume:  75     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-31     Completed Date:  2009-02-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  156-66     Citation Subset:  IM    
Affiliation:
Department of Medicine, Université de Montréal, Centre hospitalier de l'Université de Montréal Hôtel-Dieu, Research Centre, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology*,  therapeutic use
Animals
Apoptosis / drug effects*
Fibrosis / drug therapy*
Hypertension
Kidney Tubules / drug effects,  pathology*
Mice
Mice, Transgenic
NADPH Oxidase / antagonists & inhibitors
Reactive Oxygen Species / metabolism
Renin-Angiotensin System / drug effects
Grant Support
ID/Acronym/Agency:
HL-48455/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Reactive Oxygen Species; 498-02-2/acetovanillone; EC 1.6.3.1/NADPH Oxidase
Comments/Corrections
Comment In:
Kidney Int. 2009 Jan;75(2):135-7   [PMID:  19116641 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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