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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.
- 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]
- Subjects :
- URETERIC obstruction
CELL proliferation
PURINERGIC receptors
EPITHELIAL cells
APOPTOSIS
RNA metabolism
PROTEIN metabolism
MUSCLE protein metabolism
COLLAGEN
BIOCHEMISTRY
RESEARCH
KIDNEYS
FIBROBLASTS
NEPHRITIS
ANIMAL experimentation
GROWTH factors
TIME
RESEARCH methodology
NEUROTRANSMITTERS
CELL physiology
KIDNEY tubules
INTERLEUKIN-1
MACROPHAGES
FIBROSIS
MEDICAL cooperation
EVALUATION research
AMINES
RATS
PHENOMENOLOGY
CELL motility
COMPARATIVE studies
DRUGS
ANTIGENS
PHARMACODYNAMICS
DISEASE complications
Subjects
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