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Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode.

Abstract：

AIMS:Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. MAIN METHODS:Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. KEY FINDINGS:An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. SIGNIFICANCE:The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.

journal_name

Life Sci

journal_title

Life sciences

authors

Jesmin S,Shimojo N,Yamaguchi N,Mowa CN,Oki M,Zaedi S,Sultana SN,Rahman A,Islam M,Sawamura A,Gando S,Kawano S,Miyauchi T,Mizutani T

doi

10.1016/j.lfs.2014.03.013

subject

Has Abstract

pub_date

2014-05-02 00:00:00

pages

127-33

issue

2

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(14)00337-3

journal_volume

102

pub_type

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