Format

Send to:

Choose Destination
See comment in PubMed Commons below
Free Radic Biol Med. 2014 Jun;71:16-25. doi: 10.1016/j.freeradbiomed.2014.03.012. Epub 2014 Mar 19.

Role of TLR4 in lipopolysaccharide-induced acute kidney injury: protection by blueberry.

Author information

  • 1Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
  • 2Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA; Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
  • 3Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
  • 4Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: jfrancis@lsu.edu.

Abstract

Inflammation has been implicated in the pathophysiology of kidney disorders. Previous studies have documented the contributions of various inflammatory cascades in the development of kidney and other organ dysfunctions. The Toll-like receptor 4 (TLR4) inflammatory pathway is a major contributor of inflammation in the kidney. Interestingly, lipopolysaccharide (LPS), a specific ligand for TLR4, has been shown to induce acute kidney injury (AKI) in animal models. We have previously studied the beneficial effects of nonpharmacological agents, particularly blueberries (BB), in attenuating inflammation and oxidative stress. We hypothesize that BB protect against the LPS-induced AKI by inhibiting TLR4 activation and kidney injury markers. Twelve-week-old male Sprague-Dawley rats received a BB solution or saline intragastric gavage for 2 days. One group of BB and saline-gavaged animals was injected with LPS (10 mg/kg bw). Another group of rats was injected with VIPER (0.1 mg/kg iv), a TLR4-specific inhibitory peptide, 2 h before LPS administration. Compared to LPS-administered rats, the BB-pretreated animals exhibited improved glomerular filtration rate, elevated renal blood flow, and a reduced renal vascular resistance. In addition, a reduction in the rate of production of free radicals, namely total reactive oxygen species (ROS) and superoxide, was observed in the BB-supplemented LPS group. Gene and protein expressions for TLR4, proinflammatory cytokine, and acute kidney injury markers were also attenuated in animals that were pretreated with BB as measured by real time RT-PCR and Western blotting, respectively. These results in the BB-pretreated group were consistent with those in the VIPER-treated rats, and indicate that BB protects against AKI by inhibiting TLR4 and its subsequent effect on inflammatory and oxidative stress pathways.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Blueberry; Inflammation; Kidney Injury; Oxidative stress; TLR4; VIPER

PMID:
24657730
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk