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Brilliant blue G, a P2X7 receptor antagonist, attenuates early phase of renal inflammation, interstitial fibrosis and is associated with renal cell proliferation in ureteral obstruction in rats.

Authors :
Pereira, José Monteiro Sad
Barreira, André Luis
Gomes, Conrado Rodrigues
Ornellas, Felipe Mateus
Ornellas, Débora Santos
Miranda, Luiz Carlos
Cardoso, Lucio Ronaldo
Coutinho-Silva, Robson
Schanaider, Alberto
Morales, Marcelo M.
Leite, Maurilo
Takiya, Christina Maeda
Leite, Maurilo Jr
Source :
BMC Nephrology; 5/29/2020, Vol. 21 Issue 1, p1-11, 11p
Publication Year :
2020

Abstract

<bold>Background: </bold>Previous study showed that purinergic P2X7 receptors (P2X7R) reach the highest expression in the first week after unilateral ureteral obstruction (UUO) in mice, and are involved in the process of inflammation, apoptosis and fibrosis of renal tissue. We, herein, document the role of purinergic P2X7 receptors activation on the third day of UUO, as assessed by means of BBG as its selective inhibitor.<bold>Methods: </bold>We investigated the effects of brilliant blue G (BBG), a P2X7R antagonist, in the third day of kidney tissue response to UUO in rats. For this purpose, male Wistar rats submitted to UUO or sham operated, received BBG or vehicle (V), comprising four groups: UUO-BBG, UUO-V, sham-BBG and sham-V. The kidneys were harvested on day 3 UUO and prepared for histology, immunohistochemistry (P2X7R, PCNA, CD-68, α-sma, TGF-β1, Heat-shock protein-47, TUNEL assay), quantitative real-time PCR (IL-1β, procollagens type I, III, and IV) for mRNA quantification.<bold>Results: </bold>The group UUO-V presented an enhancement in tubular cell P2X7-R expression, increase influx of macrophages and myofibroblasts, HSP-47 and TGF- β1 expression. Also, upregulation of procollagen types I, III, and IV, and IL-1β mRNAs were seen. On the other hand, group UUO-BBG showed lower expression of procollagens and IL-1β mRNAs, as well as less immunoreactivity of HSP-47, TGF-β, macrophages, myofibroblasts, and tubular apoptosis. This group also presented increased epithelial cell proliferation.<bold>Conclusion: </bold>BBG, a known highly selective inhibitor of P2X7R, attenuated renal inflammation, collagen synthesis, renal cell apoptosis, and enhanced renal cell proliferation in the early phase of rat model of UUO. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14712369
Volume :
21
Issue :
1
Database :
Complementary Index
Journal :
BMC Nephrology
Publication Type :
Academic Journal
Accession number :
143491907
Full Text :
https://doi.org/10.1186/s12882-020-01861-2