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@article{Tam:2018:10.14814/phy2.13622,
author = {Tam, FWK and Arulkumaran, N and Sixma, M and Ceravola, E and Jentho, E and Prendecki, M and Bass, P and unwin, RJ and Singer, M},
doi = {10.14814/phy2.13622},
journal = {Physiological Reports},
pages = {e13622--e13622},
title = {P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis},
url = {http://dx.doi.org/10.14814/phy2.13622},
volume = {6},
year = {2018}
}

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TY  - JOUR
AB  - Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATPsensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluidresuscitated 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 timepoints were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis. Compared with shamoperated 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 IL1β (0(0–10)(pg/mL) vs. 1671(1445–33778)(pg/mL); P < 0.001) and renal IL1β (86(50–102)pg/mg protein vs. 200 (147–248)pg/mg protein; P = 0.0031) were significantly elevated in septic compared with shamoperated animals at 6 h. Serum creatinine was elevated in septic animals compared with shamoperated animals at 24 h (23(22–25) μmol/L vs. 28 (25–30)μmol/L; P = 0.0321). Renal IL1β levels were significantly lower in A438079treated animals compared with untreated animals at 6 h (70(55–128)pg/mg protein vs. 200(147–248)pg/mg protein; P = 0.021). At 24 h, compared with untreated animals, A438079treated animals had more rapid resolution of tachycardia (22(13–36)% vs. −1(−6 to 7)%; P = 0.019) and fever (39.0(38.6–39.1)°C vs. 38.2(37.6–38.7)°C; 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
AU  - Tam,FWK
AU  - Arulkumaran,N
AU  - Sixma,M
AU  - Ceravola,E
AU  - Jentho,E
AU  - Prendecki,M
AU  - Bass,P
AU  - unwin,RJ
AU  - Singer,M
DO  - 10.14814/phy2.13622
EP  - 13622
PY  - 2018///
SN  - 2051-817X
SP  - 13622
TI  - P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis
T2  - Physiological Reports
UR  - http://dx.doi.org/10.14814/phy2.13622
UR  - http://hdl.handle.net/10044/1/57094
VL  - 6
ER  -

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