Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats

Figure 1 Effects of α-lipoic acid on hepatic triglyceride contents. Hepatic triglyceride levels were measured from the blood of each group of fructose-fed rats and the control group. Values are expressed as mean ± SE, n = 6 per group, ^aP < 0.05 vs C_PV. C: Regular diet; F: High-fructose enriched diet; LA: Lipoic acid; LPS: Lipopolysaccharides.

Figure 2 Effect of α-lipoic acid on portal endotoxemia-induced changes in hepatic oxidative and inflammatory markers. The following parameters were measured from liver of each group of fructose-fed rats and the control group: (A) Malondialdehyde (MDA) content; (B) Glutathione (GSH) content; (C) Toll-like receptor 4 (TLR4) gene expression; (D) Tumor necrosis factor alpha (TNF-α) protein; and (E) Interleukin-6 (IL-6) protein. Values are expressed as mean ± SE, n = 6 per group. ^aP < 0.05 vs C_PV; ^cP < 0.05 vs F_PV; ^eP < 0.05 vs F_PLPS. C: Regular diet; F: High-fructose enriched diet; LA: Lipoic acid; LPS: Lipopolysaccharides.

Figure 3 Histopathological examination of liver in rats with regular or high-fructose feeding. Lipid accumulation in: (A) C_PV rats; (B) F_PV rats; (C)F_{PV + LA}; (D) F_PLPS; and (E) F_{PLPS + LA} rats. CD-68 positive cell infiltration in: (F) C_PV rats; (G) F_PV rats; (H) F_{PV + LA}; (I) F_PLPS; and (J) F_{PLPS + LA} rats. Slides were stained with hematoxylin and eosin (A-E) and immunostained with an anti-CD68 antibody (F-J). Arrows indicate CD68 positive cells. C: Regular diet; F: High-fructose enriched diet; LA: Lipoic acid; LPS: Lipopolysaccharides; CV: Central vein.

Figure 4 Effect of α-lipoic acid on portal endotoxemia-induced changes in the pancreas. The pancreata from experimental animals were harvested and tested for: (A) Malondialdehyde (MDA) content; (B) Tumor necrosis factor alpha (TNF-α) protein level; and (C) Interleukin-6 (IL-6) protein level. Values are expressed as mean ± SE, n = 6 per group. ^aP < 0.05 vs C_PV; ^cP < 0.05 vs F_PV; ^eP < 0.05 vs F_PLPS. C: Regular diet; F: High-fructose enriched diet; LA: Lipoic acid; LPS: Lipopolysaccharides.

Figure 5 Histopathologicalexamination of pancreatic islets. A: Tissue samples from each subset of animals were analyzed by hematoxylin and eosin (HE) staining (a-C_PV, b-F_PV, c-F_{PV + LA}, d-F_PLPS, e-F_{PLPS + LA}) and immunostaining with an antibody against CD68 (f-C_PV, g-F_PV, h-F_{PV + LA}, i-F_PLPS, j-F_{PLPS + LA}); This data was then quantitated as (B) percentage of islets infiltrated and (C) number of CD68+ cells per islet. Arrows indicated CD68-positive cells. I: Islet. A total of 100 ± 25 islets per experimental group were blindly scored for CD68-positive cells around the periphery and/or within islets from 5 to 6 different animals. Islet area was measured by the area of islet capsule in pancreatic section with HE stain and computed using AxioVision LE 4.8.2.0 software. Values are expressed as mean ± SE, n = 6 per group. Line bar: 50 μm. ^aP < 0.05 vs C_PV; ^cP < 0.05 vs F_PV; ^eP < 0.05 vs F_PLPS. C: Regular diet; F: High-fructose enriched diet; LA: Lipoic acid; LPS: Lipopolysaccharides.

Figure 6 Effect of α-lipoic acid on plasma glucose and insulin levels. A hyperglycemic clamp technique was used to evaluate glucose-stimulated insulin secretion. A: Plasma glucose levels during the clamp period; B: Change in insulin levels during clamp period; C: The insulin level averages during the first phase (0-10 min) and the second phase (10-240 min) of the clamp period. Values are expressed as mean ± SE, n = 6 per group. ^aP < 0.05 vs C_PV; ^cP < 0.05 vs F_PV; ^eP < 0.05 vs F_PLPS. C: Regular diet; F: High-fructose enriched diet; LA: Lipoic acid; LPS: Lipopolysaccharides.