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

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posted on 28.02.2018 by Nishkantha Arulkumaran, Marije Sixma, Sean Pollen, Elias Ceravola, Elisa Jentho, Maria Pendrecki, Paul Bass, Robert Unwin, Frederick Tham, Mervyn Singer
Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome 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 hour 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 2h following induction of sepsis. Compared with sham-operated animals, septic animals had significant increases in heart rate (-1(-4–8)% vs. 21(12-26)%; p=0.003)), fever (37.4(37.2-37.6)oC vs. 38.6(38.2-39.0)oC; p=0.0009), and falls in serum albumin (29(27-30)g/l vs. 26(24-28); p=0.0242). Serum IL-1 (0(0-10)(pg/ml) vs. 1671(1445-33778)(pg/ml); p<0.001) and renal IL-1 (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 6h. Serum creatinine was elevated in septic animals compared with sham-operated animals at 24h (23(22-25)mol/l vs. 28 (25-30)mol/l; p=0.0321). Renal IL-1 levels were significantly lower in A-438079-treated animals compared with untreated animals at 6h (70(5-128)pg/mg protein vs. 200(147-248)pg/mg protein; p=0.021). At 24h, compared with untreated animals, A-438079-treated animals had more rapid resolution of tachycardia (22(13-36)% vs. -1(-6-7)%; p=0.019) and fever (39.0(38.6-39.1)oC vs. 38.2(37.6-38.7)oC; p<0.024), higher serum albumin (23(21-25)g/l vs. (27(25-28)g/l); p=0.006), lower arterial lactate (3.2(2.5-4.3)mmol/l vs.1.4(0.9-1.8)mmol/l; p=0.037), and lower serum creatinine concentrations (28(25-30)mol/l vs.22(17-27)mol/l; p=0.019). P2X7A treatment ameliorates the systemic inflammatory response and renal dysfunction in this clinically relevant model of sepsis-related AKI.

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