title: Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats.
abstract: OBJECTIVE
  To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats.
  
  
  METHODS
  Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (FPV), with intraportal saline plus administration of LA (FPV + LA), with lipopolysaccharide (LPS) infusion (FPLPS), and with LPS infusion plus administration of LA (FPLPS + LA). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry.
  
  
  RESULTS
  Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration.
  
  
  CONCLUSIONS
  These data suggest LA could significantly suppress mild portal-endotoxemia but not fructose-induced liver and pancreatic abnormalities in a rodent model for metabolic syndrome.
authors.affiliation: Division of General Surgery, Department of Surgery, Yung Kung Campus, Chi-Mei Medical Center, Tainan 710, Taiwan.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Tian
authors.forename: Chih-Tsueng
authors.initials: CT
authors.lastname: He
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Po-Shiuan
authors.initials: PS
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D005234:Fatty Liver / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005632:Fructose; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000097:blood; D008063:Thioctic Acid / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D008070:Lipopolysaccharides; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D013481:Superoxides; D005632:Fructose; D008315:Malondialdehyde; D008063:Thioctic Acid; D005978:Glutathione
keywords: Fructose; Insulin secretion; Lipoic acid; Oxidative stress; Portal endotoxemia; Steatohepatitis