title: P38 MAPK Pharmacological Inhibitor SB203580 Alleviates Total Parenteral Nutrition-Induced Loss of Intestinal Barrier Function but Promotes Hepatocyte Lipoapoptosis.
abstract: OBJECTIVE
  Our previous studies have provided evidence that p38 mitogen-activated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease.
  
  
  METHODS
  A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications.Intestinal barrier function was evaluated by transepithelial electrical resistance (TER) and paracellular permeability in Caco-2 cells. The palmitic acid (PA) was used to induce hepatic lipoapoptosis in vitro. The lipoapoptosis was detected using Caspase-3/7 and lipid staining.
  
  
  RESULTS
  In the present study, we showed that SB203580 treatment significantly suppressed TPN-mediated intestinal permeability in rats. SB203580 treatment significantly inhibited IL-1β-induced an increase in tight junction permeability of Caco-2 cells via repressing the p38/ATF-2 signaling. Unexpectedly, SB203580 treatment enhanced hepatic lipoapoptosis in the model of TPN. Palmitic acid (PA)-induced hepatic lipoapoptosis in human liver cells was significantly augmented by the SB203580 treatment.
  
  
  CONCLUSIONS
  We demonstrate that the p38 MAPK inhibitor SB203508 ameliorates intestinal barrier function but promotes hepatic lipoapoptosis in model of TPN.
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Xiao
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Yan
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.forename: Jun-Kai
authors.initials: JK
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D051698:Activating Transcription Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D023421:Models, Animal; D019308:Palmitic Acid / Q000633:toxicity; D010289:Parenteral Nutrition, Total; D010539:Permeability / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D007093:Imidazoles; D053583:Interleukin-1beta; D011725:Pyridines; D019308:Palmitic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053179:Caspase 7; C093642:SB 203580
keywords: Intestinal barrier; Lipoapoptosis; P38 MAPK; SB203580; Total parenteral nutrition