In several earlier studies, BBG, a selective P2X7R antagonist, was used like a potent inhibitor of P2X7R that reduces inflammation, immune cells activation, and fibrosis [10, 18, 19]. Wistar rats submitted to UUO or sham managed, 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, -sma, TGF-1, Heat-shock protein-47, TUNEL assay), quantitative real-time PCR (IL-1, procollagens type I, III, and IV) for mRNA quantification. Results The group UUO-V offered an enhancement in tubular cell P2X7-R expression, increase influx of macrophages and myofibroblasts, HSP-47 and TGF- 1 expression. Also, upregulation of procollagen types I, III, and IV, and IL-1 mRNAs were seen. On the other hand, group UUO-BBG showed lower expression of procollagens and IL-1 mRNAs, as well as less immunoreactivity of HSP-47, TGF-, macrophages, myofibroblasts, and tubular apoptosis. This group also offered increased epithelial cell proliferation. Conclusion 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. strong class=”kwd-title” Keywords: Renal inflammation, P2X7 receptor, Unilateral ureteral obstruction, Macrophages Background Adenosine triphosphate (ATP) is a multifunctional nucleotide, released by hurt/dying cells, and is the principal agonist for purinergic P2 receptors [1]. These receptors are divided into metabotropic G protein-coupled P2Y (P2YR) and ionotropic ligand gated P2X (P2XR). P2X are ligand-gated ion channels for Na+, Ca?+?and K+, SCDO3 known as ionotropic. Currently, seven subtypes of P2X receptors have been cloned and identified as P2X1C7 [2]. P2X7R are ATP-gated nonselective ion channels, permeable to Na+, K+, and Ca2+, expressed in a wide range of epithelial, endothelial, mesenchymal and immune cells. They are ubiquitously expressed in cortex and medulla, in vascular and tubular compartments [3]. P2X7R is usually scantly expressed in renal tissue in normal conditions, but can be upregulated in disease says Nafamostat mesylate [4, 5]. P2XR-ATP axis is important in homeostasis of diverse physiological and pathophysiological processes, including hypertension [6], diabetes [7, 8], polycystic kidney disease [9], inflammatory, and autoimmune disorders [10]. The activation of P2X7Rs may be involved in renal diseases and are common in renal compartments, expressed in immune cells, fibroblasts and myofibroblasts, upregulated in inflammation, and associated with the production of pro-inflammatory mediators [11, 12]. The progression of chronic kidney disease (CKD) is related to the intensity of renal interstitial Nafamostat mesylate fibrosis, the accumulation of extracellular matrix proteins and the process of renal cell death [13]. The importance of P2X7R in renal tissue fibrosis has been highlighted on P2X7R knockout mice submitted to UUO, a well-known model of tubulointerstitial fibrosis [5]. In the present study, we attempted to investigate the effect of BBG, a selective P2X7R antagonist, on the early development of renal injury after UUO in rats, in order to better elucidate the role of purinergic signaling antagonism around the processes of renal inflammation, fibrosis, renal cells apoptosis and regenerative proliferation in this setting. Methods Forty male adult Wistar rats were housed under specific pathogen-free conditions, with controlled heat and relative humidity, and provided standard rat chow and water ad libitum. This study was approved by the Animals Ethics Committee from the Health Sciences Center, Federal University or college of Rio de Janeiro and is in compliance with the guidelines as recommended by the National Research Councils criteria (NIH No. 86C23). Experimental protocol Rats were randomly divided into four groups of 5 animals each. Two groups were submitted to a total UUO and received BBG (UUO-BBG) or vehicle (UUO-V). The other two groups, SHAM-operated, received BBG or vehicle (SHAM-BBG or Nafamostat mesylate SHAM-V, respectively). Surgical procedure Animals were anesthetized with Nafamostat mesylate ketamine (35?mg/kg) and xylazine (9?mg/kg) by peritoneal route. An abdominal midline incision was carried out and the left ureter was ligated at two points using 4C0 silk and sectioned. BBG (Amazing Blue G), 40?mg/kg (Sigma-Aldrich, Saint Louis, MO, USA, cat. B0770) was dissolved in 0.2% dimethyl sulfoxide (DMSO, Sigma-Aldrich, cat. D2650) in sterile saline answer and was injected in the substandard cava vein (0.5?mL) after ureteral ligation Nafamostat mesylate (Group UUO-BBG). In another group, obstructed rats received vehicle instead of BBG (Group UUO-V). The abdominal wall was closed.