P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis

Physiological Reports
Nishkantha ArulkumaranMervyn Singer

Abstract

Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis. Compared with sham-operated animals, septic animals had significant increases in heart rate (-1(-4 to 8)% vs. 21(12-26)%; P = 0.003), fever (37.4(37.2-37.6)°C vs. 38.6(38.2-39.0)°C; P = 0.0009), and falls in serum albumin (29(27-30)g/L vs. 26(24-28); P = 0.0242). Serum IL-1β (0(0-10)(pg/mL) vs. 1671(1445-33778)(pg/mL); P < 0.001) and renal IL-1β (86(50-102)pg/mg protein vs. 200 (147-248)pg/mg protein; P = 0.0031) were significantly elevated in septic compared with sham-operated animals at 6 h. Serum creatinine was elevated in septic animals compared with sham-operated animals at 24 h (23(22-25) μmol/L vs. 28 (25...Continue Reading

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Citations

Aug 23, 2019·Physiological Reviews·Volker VallonBellamkonda K Kishore
Jun 18, 2019·Oxidative Medicine and Cellular Longevity·Sicheng LiJianan Ren
Aug 21, 2019·Mediators of Inflammation·Jinjin FanXueqing Yu
Sep 26, 2020·Frontiers in Medicine·Vikram SabapathyRahul Sharma
Apr 27, 2021·Frontiers in Immunology·Jean M KanellopoulosDavid M Ojcius

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