title: Role of TLR4 in lipopolysaccharide-induced acute kidney injury: protection by blueberry.
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.
authors.affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Anand R
authors.initials: AR
authors.lastname: Nair
authors.affiliation: Comparative 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.
authors.forename: Gustavo S
authors.initials: GS
authors.lastname: Masson
authors.affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ebenezer
authors.affiliation: Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Piero
authors.affiliation: Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: jfrancis@lsu.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D029798:Blueberry Plants / Q000737:chemistry*; D015870:Gene Expression; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D010455:Peptides / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D010455:Peptides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4
keywords: Blueberry; Inflammation; Kidney Injury; Oxidative stress; TLR4; VIPER