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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression
Journal of Hepatology, Volume 56, No. 5, Year 2012
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Description
Background & Aims: Superimposed infection and/or inflammation precipitate renal failure in cirrhosis. This study aimed at testing the hypothesis that increased gut bacterial translocation in cirrhosis primes the kidney to the effect of superimposed inflammation by upregulating expression of Toll-like receptor 4 (TLR4), NFκB, and cytokines. A well-characterized bile-duct ligated (BDL) model of cirrhosis, which develops renal failure following superimposed inflammatory insult with lipopolysaccharide (LPS), was used and selective gut decontamination was performed using norfloxacin. Methods: Sprague-Dawley rats were studied: Sham, Sham + LPS; BDL, BDL + LPS; an additional BDL and BDL + LPS groups were selectively decontaminated with norfloxacin. Plasma biochemistry, plasma renin activity (PRA) and cytokines and, protein expression of TLR4, NFκB, and cytokines were measured in the kidney homogenate. The kidneys were stained for TLR4, TLR2, and caspase-3. Endotoxemia was measured using neutrophil burst and Limulus amoebocyte lysate (LAL) assays. Results: The groups treated with norfloxacin showed significant attenuation of the increase in plasma creatinine, plasma and renal TNF-α and renal tubular injury on histology. The increased renal protein expression of TLR4, NFκB, and caspase-3 in the untreated animals was significantly attenuated in the norfloxacin treated animals. PRA was reduced in the treated animals and severity of endotoxemia was also reduced. Conclusions: The results show for the first time that kidneys in cirrhosis show an increased expression of TLR4, NFκB, and the pro-inflammatory cytokine TNF-α, which makes them susceptible to a further inflammatory insult. This increased susceptibility to LPS can be prevented with selective decontamination, providing novel insights into the pathophysiology of renal failure in cirrhosis. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Authors & Co-Authors
Shah, Naina
United Kingdom, London
The Royal Free Hospital
Dhar, Dipok Kumar
United Kingdom, London
The Royal Free Hospital
Mohamed, Fatma El Zahraa
United Kingdom, London
The Royal Free Hospital
Egypt, Minya
Minia University
Habtesion, Abeba
United Kingdom, London
The Royal Free Hospital
Davies, Nathan A.
United Kingdom, London
The Royal Free Hospital
Jover-Cobos, Maria
United Kingdom, London
The Royal Free Hospital
MacNaughtan, Jane
United Kingdom, London
The Royal Free Hospital
Sharma, Vikram
United Kingdom, London
The Royal Free Hospital
Olde-Damink, Steven W.M.
United Kingdom, London
The Royal Free Hospital
Netherlands, Maastricht
Universiteit Maastricht
Mookerjee, Rajeshwar Prosad
United Kingdom, London
The Royal Free Hospital
Jalan, Rajiv
United Kingdom, London
The Royal Free Hospital
Statistics
Citations: 114
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1016/j.jhep.2011.11.024
ISSN:
01688278
Research Areas
Violence And Injury