title: Pretreatment of Sialic Acid Efficiently Prevents Lipopolysaccharide-Induced Acute Renal Failure and Suppresses TLR4/gp91-Mediated Apoptotic Signaling.
abstract: OBJECTIVE
  Lipopolysaccharides (LPS) binding to Toll-like receptor 4 (TLR4) activate NADPH oxidase gp91 subunit-mediated inflammation and oxidative damage. Recognizing the high binding affinity of sialic acid (SA) with LPS, we further explored the preventive potential of SA pretreatment on LPS-evoked acute renal failure (ARF).
  
  
  METHODS
  We determined the effect of intravenous SA 30 min before LPS-induced injury in urethane-anesthetized female Wistar rats by evaluating kidney reactive oxygen species (ROS) responses, renal and systemic hemodynamics, renal function, histopathology, and molecular mechanisms.
  
  
  RESULTS
  LPS time-dependently reduced arterial blood pressure, renal microcirculation, and increased blood urea nitrogen and creatinine in the rats. LPS enhanced monocyte/macrophage infiltration and ROS production, and subsequently impaired kidneys with the enhancement of TLR4/NADPH oxidase gp91/Caspase 3/poly-(ADP-ribose)-polymerase (PARP)-mediated apoptosis in the kidneys. SA pretreatment effectively alleviated LPS-induced ARF. The levels of LPS-increased ED-1 infiltration and ROS production in the kidney were significantly depressed by SA pretreatment. Furthermore, SA pretreatment significantly depressed TLR4 activation, gp91 expression, and Caspase 3/PARP induced apoptosis in the kidneys.
  
  
  CONCLUSIONS
  We suggest that pretreatment of SA significantly and preventively attenuated LPS-induced detrimental effects on systemic and renal hemodynamics, renal ROS production and renal function, as well as, LPS-activated TLR4/gp91/Caspase3 mediated apoptosis signaling.
authors.affiliation: Renal Division, Department of Internal Medicine, Far Eastern Memory Hospital, New Taipei City, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Hsu
authors.forename: Chin-Chih
authors.initials: CC
authors.lastname: Chen
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D007668:Kidney / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D019158:N-Acetylneuraminic Acid