Published online May 14, 2013. doi: 10.3748/wjg.v19.i18.2761
Revised: February 11, 2013
Accepted: February 28, 2013
Published online: May 14, 2013
AIM: 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.
CONCLUSION: 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.
Core tip:α-lipoic acid (LA), a potent antioxidant and also an inducer of endogenous antioxidants has been reported to protect the liver and pancreas from injury. Our observations suggest that LA could significantly suppress inflammatory change of steatosis induced by low-dose intraportal lipopolysaccharide infusion and associated deterioration of insulin secretion in this metabolic syndrome rodent model. In addition, our data suggest that hepatic toll-like receptor 4 signaling might not only play a significant role in chronic fructosefeeding-induced hepatic steatosis but also in its subacute inflammatory change induced by mild portal endotoxemia and associated extrahepatic disorders.