Abstract | BACKGROUND & AIMS: 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.
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Authors | Naina Shah, Dipok Dhar, Fatma El Zahraa Mohammed, Abeba Habtesion, Nathan A Davies, Maria Jover-Cobos, Jane Macnaughtan, Vikram Sharma, Steven W M Olde Damink, Rajeshwar P Mookerjee, Rajiv Jalan |
Journal | Journal of hepatology
(J Hepatol)
Vol. 56
Issue 5
Pg. 1047-1053
(May 2012)
ISSN: 1600-0641 [Electronic] Netherlands |
PMID | 22266601
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Anti-Bacterial Agents
- Cytokines
- Lipopolysaccharides
- NF-kappa B
- Tlr4 protein, rat
- Toll-Like Receptor 4
- Renin
- Norfloxacin
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Topics |
- Acute Kidney Injury
(metabolism, prevention & control)
- Animals
- Anti-Bacterial Agents
(pharmacology)
- Cytokines
(metabolism)
- Disease Models, Animal
- Gastrointestinal Tract
(drug effects, microbiology)
- Kidney
(metabolism)
- Lipopolysaccharides
(adverse effects)
- Liver Cirrhosis
(complications, metabolism)
- Male
- NF-kappa B
(metabolism)
- Norfloxacin
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Renin
(blood)
- Toll-Like Receptor 4
(metabolism)
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