Document Detail


Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro.
MedLine Citation:
PMID:  20375980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiproteinuric properties, we established an experimental rat model of passive Heymann nephritis and a C5b-9 injury model of podocytes in vitro. Treatment or pretreatment with triptolide markedly reduced established proteinuria as well as the titer of circulating rat anti-rabbit IgG antibodies in these nephritic rats, accompanied by a reduction in glomerular C5b-9 deposits. Expression of desmin, a marker of podocyte injury, diminished after triptolide treatment, whereas quantitative analysis of mean foot process width showed that effacement of foot processes was substantially reversed. In in vitro studies we found that triptolide deactivated NADPH oxidase, suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase, and restored RhoA signaling activity. Triptolide did not interfere with the formation of C5b-9 on the membrane of podocytes. Thus, triptolide reduces established heavy proteinuria and podocyte injuries in rats with passive Heymann nephritis, and protects podocytes from C5b-9-mediated injury.
Authors:
Zhao-Hong Chen; Wei-Song Qin; Cai-Hong Zeng; Chun-Xia Zheng; Yi-Mei Hong; Yi-Zhou Lu; Lei-Shi Li; Zhi-Hong Liu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-10
Journal Detail:
Title:  Kidney international     Volume:  77     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-14     Completed Date:  2010-08-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  974-88     Citation Subset:  IM    
Affiliation:
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Cell Line
Complement Membrane Attack Complex / immunology*
Cytoprotection
Desmin / metabolism
Disease Models, Animal
Diterpenes / administration & dosage,  adverse effects,  pharmacology*
Epoxy Compounds / administration & dosage,  adverse effects,  pharmacology
Female
Glomerulonephritis, Membranous / drug therapy*,  immunology,  pathology
Heymann Nephritis Antigenic Complex / immunology
Immunoglobulin G / blood
Immunosuppressive Agents / administration & dosage,  adverse effects,  pharmacology*
Mice
NADPH Oxidase / metabolism
Phenanthrenes / administration & dosage,  adverse effects,  pharmacology*
Podocytes / drug effects*,  immunology,  pathology
Proteinuria / immunology,  pathology,  prevention & control*
Rabbits
Rats
Rats, Sprague-Dawley
Rats, Wistar
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects
Tacrolimus / pharmacology
Time Factors
p38 Mitogen-Activated Protein Kinases / metabolism
rho GTP-Binding Proteins / metabolism
Chemical
Reg. No./Substance:
0/Complement Membrane Attack Complex; 0/Desmin; 0/Diterpenes; 0/Epoxy Compounds; 0/Heymann Nephritis Antigenic Complex; 0/Immunoglobulin G; 0/Immunosuppressive Agents; 0/Phenanthrenes; 0/Reactive Oxygen Species; 109581-93-3/Tacrolimus; 38748-32-2/triptolide; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.6.5.2/RhoA protein, mouse; EC 3.6.5.2/rho GTP-Binding Proteins

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