title: α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and β cell dysfunction.
abstract: BACKGROUND
  This study was undertaken to evaluate the preventive effect of α-lipoic acid (LA) on chronic mild portal endotoxaemia-mediated subacute hepatic inflammation and pancreatic β cell dysfunction in rats.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly assigned into four groups: those with intraportal vehicle (saline) or low-dose lipopolysaccharide (LPS) (0·42 ng/kg/min) infusion, combined with oral administration of vehicle or LA, a potent antioxidant (60 mg/kg/day) for 4 weeks. The hyperglycaemic clamp and euglycaemic clamp techniques were used to access the glucose-stimulated insulin secretion and systemic insulin sensitivity in vivo.
  
  
  RESULTS
  Body weight, fasting plasma glucose and insulin were not different among groups. In rats with chronic intraportal LPS infusion, plasma C-reactive protein, amylase, superoxide levels, the contents of thiobarbituric acid-reactive substance, tumour necrosis factor α and interleukin 6 in liver and pancreas and also the gene expression of Toll-like receptor 4 in liver were significantly increased as compared with those with LA cotreatment. The histopathological examination showed that inflammatory changes were clearly visible in liver and pancreatic islets of LPS-infused rats and rarely observed in those cotreated with LA. In addition, low-dose intraportal LPS infusion also significantly impaired glucose-stimulated insulin secretion but not affect the systemic insulin sensitivity and metabolic clearance rate of insulin. LA administration markedly reversed LPS-induced β cell dysfunction.
  
  
  CONCLUSIONS
  α-Lipoic acid cotreatment could significantly prevent mild portal endotoxaemia-induced chronic hepatic inflammation and impaired pancreatic insulin secretion in absence of changing systemic insulin resistance.
authors: Division of General Surgery, Department of Surgery, Yung Kung Campus, Chi-Mei Medical Center, Tainan, Taiwan.
authors: Yu-Feng
authors: YF
authors: Tian
authors: Chang-Hsun
authors: CH
authors: Hsieh
authors: Yen-Ju
authors: YJ
authors: Hsieh
authors: Yu-Ting
authors: YT
authors: Chen
authors: Yi-Jen
authors: YJ
authors: Peng
authors: Po-Shiuan
authors: PS
authors: Hsieh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control* / Q000628:therapy; D019446:Endotoxemia / Q000517:prevention & control*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects; D011168:Portal System / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008063:Thioctic Acid