PMID- 25143459
OWN - NLM
STAT- MEDLINE
DCOM- 20150303
LR  - 20181202
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 307
IP  - 8
DP  - 2014 Oct 15
TI  - Semicarbazide-sensitive amine oxidase (SSAO) inhibition ameliorates kidney 
      fibrosis in a unilateral ureteral obstruction murine model.
PG  - F908-16
LID - 10.1152/ajprenal.00698.2013 [doi]
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme known for its dual 
      function in mediating inflammation and reactive oxygen species production. 
      However, the role of SSAO inhibitors in limiting kidney fibrosis is unclear. We 
      aimed to determine the effectiveness of a SSAO inhibitor (SSAOi; PXS4728A) as an 
      antifibrotic agent using a 7-day unilateral ureteric obstruction (UUO) model of 
      acute kidney fibrosis in 6- to 8-wk-old mice. The experimental groups were 1) 
      Sham operated; 2) UUO; 3) UUO+SSAOi (2 mg/kg); 4) UUO+telmisartan, an angiotensin 
      receptor blocker (3 mg/kg); and 5) UUO+SSAOi+telmisartan. Kidney tissue was 
      analyzed for histological evidence of tubulointerstitial fibrosis, nitrotyrosine 
      staining, and mRNA expression of markers associated with fibrosis and 
      inflammation. Kidney SSAO activity was determined by radiometric 
      [(14)C]benzylamine methodology. Our results show that SSAOi effectively 
      suppresses UUO-mediated SSAO activity. Extracellular matrix markers, namely, 
      fibronectin, collagen IV protein, and nitrotyrosine staining, were lower in 
      UUO+SSAOi mice compared with untreated UUO mice. This was consistent with the 
      attenuated mRNA expression of collagen IV and fibronectin. SSAOi effectively 
      inhibited transforming growth factor-beta1 (TGF-beta1) and monocyte chemoattractant 
      protein-1 (MCP-1) expression to a similar extent to that observed with 
      telmisartan. Individually, SSAOi and telmisartan induced a reduction in 
      interstitial leukocyte and macrophage accumulation. However, the combination of 
      SSAOi and telmisartan was more effective at reducing inflammatory cell 
      infiltration. These results demonstrate that SSAO inhibition significantly 
      suppresses profibrotic and proinflammatory cytokine secretion, reduces oxidative 
      stress, and limits inflammatory cell accumulation and extracellular matrix 
      expression in an acute model of renal fibrosis.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Wong, May
AU  - Wong M
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia;
FAU - Saad, Sonia
AU  - Saad S
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia;
FAU - Zhang, Jie
AU  - Zhang J
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia;
FAU - Gross, Simon
AU  - Gross S
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia;
FAU - Jarolimek, Wolfgang
AU  - Jarolimek W
AD  - Pharmaxis, Limited, Frenchs Forest, Sydney, New South Wales, Australia; and.
FAU - Schilter, Heidi
AU  - Schilter H
AD  - Pharmaxis, Limited, Frenchs Forest, Sydney, New South Wales, Australia; and.
FAU - Chen, Jason A
AU  - Chen JA
AD  - Department of Anatomical Pathology, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia.
FAU - Gill, Anthony J
AU  - Gill AJ
AD  - Department of Anatomical Pathology, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia.
FAU - Pollock, Carol A
AU  - Pollock CA
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia; 
      carol.pollock@sydney.edu.au.
FAU - Wong, Muh Geot
AU  - Wong MG
AD  - Kolling Institute of Medical Research, Royal North Shore Hospital, University of 
      Sydney, St. Leonards, Sydney, New South Wales, Australia;
LA  - eng
PT  - Journal Article
DEP - 20140820
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoates)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Semicarbazides)
RN  - 37QUC23K2X (carbamylhydrazine)
RN  - EC 1.4.3.21 (Amine Oxidase (Copper-Containing))
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - Amine Oxidase (Copper-Containing)/*antagonists & inhibitors
MH  - Animals
MH  - Benzimidazoles/pharmacology
MH  - Benzoates/pharmacology
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibrosis
MH  - Kidney/*pathology
MH  - Kidney Diseases/*drug therapy/enzymology/pathology
MH  - Mice, Inbred C57BL
MH  - Semicarbazides/pharmacology
MH  - Telmisartan
MH  - Ureteral Obstruction/pathology
OTO - NOTNLM
OT  - anti-inflammatory
OT  - semicarbazide-sensitive amine oxidase
OT  - tubulointerstitial fibrosis
OT  - unilateral ureteral obstruction murine model
EDAT- 2014/08/22 06:00
MHDA- 2015/03/04 06:00
CRDT- 2014/08/22 06:00
PHST- 2014/08/22 06:00 [entrez]
PHST- 2014/08/22 06:00 [pubmed]
PHST- 2015/03/04 06:00 [medline]
AID - ajprenal.00698.2013 [pii]
AID - 10.1152/ajprenal.00698.2013 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2014 Oct 15;307(8):F908-16. doi: 
      10.1152/ajprenal.00698.2013. Epub 2014 Aug 20.