Effect of a carbohydrate-containing late-evening snack on energy metabolism and fasting substrate utilization in adults with acute-on-chronic liver failure due to Hepatitis B.

BACKGROUND/OBJECTIVES: This study investigates the effects of a carbohydrate (CHO; lotus-root starch) predominant, late-evening snack (LES), containing 200 kcal (50 g CHO) on fasting resting energy expenditure (REE) and nutrient oxidation in hospitalized adults with acute-on-chronic liver failure (ACLF). SUBJECTS/METHODS: Adults with ACLF were randomized to receive daily LES (treatment; n=35) or standard care (n=35; non-supplemented control) for 14 days. REE and respiratory quotient (RQ) were measured by indirect calorimetry, nutrient oxidation (CHO, protein and fat), intake and biochemical parameters were measured in both groups at baseline and after 14 days using validated techniques. Disease severity was measured using the model for end-stage liver disease (MELD). RESULTS: No significant differences in macronutrient intake, anthropometric, demographic characteristics or MELD scores were observed between groups at baseline (P>0.05). Fasting RQ was significantly higher in the LES supplemented verses the control group after 2 weeks (P=0.02). CHO oxidation was significantly higher (P=0.001) and fat oxidation (P=0.02) was lower in the LES-supplemented group when compared with controls after 2 weeks. Fasting RQ and REE in the LES-supplemented group increased significantly (0.83 verses 0.88; P=0.007/1301±409 vs 1687±718 kcal/day; P=0.02) in patients with MELD scores 30 when compared with patients with MELD scores >30 (0.82 verses 0.84; P=0.27/ 1361±405 vs 1437±429 kcal/day; P=0.67) after supplementation. CONCLUSIONS: A carbohydrate-predominant LES is associated with increases in fasting carbohydrate oxidation, REE and reductions in fat oxidation in adults with ACLF. Therapeutic strategies utilizing LES may promote improved nutritional status in adults with ACLF.

Hepatoprotective effect and mechanistic insights of deoxyelephantopin, a phyto-sesquiterpene lactone, against fulminant hepatitis.

Deoxyelephantopin (DET) is an abundant sesquiterpene lactone isolated from an anecdotally hepatoprotective phytomedicine, Elephantopus scaber. Our objective in this study was to provide scientific evidence for the in vivo efficacy and the underlying mechanisms of action of DET in lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced fulminant hepatitis. We investigated both the protective effect of pretreatment with DET (10 mg/kg body weight, Pre-DET10) prior to administration of LPS/D-GalN and the therapeutic effect of treatment with 10 mg/kg DET (Post-DET10) or the hepatoprotective drug silymarin (Post-SM10) following the administration of LPS/D-GalN. Our data showed that Pre-DET10 prevented LPS/D-GalN-induced infiltration of F4/80 monocytes/macrophages and an increase of nitrotyrosine and cyclooxygenase-2 protein in liver tissues. Further, Post-DET10 and Psot-SM10 treatments protected against liver cell apoptosis. All three treatments suppressed serum aminotransferase activities, tumor necrosis factor-alpha and interleukin-6 levels, and serum and hepatic matrix metalloproteinase-9 activity. The Pre-DET10 or Post-DET10 and Post-SM10 treatments in combination with inhibition of heme oxygenase-1 expression ultimately decreased protection of mice from LPS/D-GalN-induced mortality, with decreased survival from 75% and 62.5% to 50%, respectively. Results obtained from serial liver scintigraphy with (99m)Tc-diisopropyl iminodiacetic acid (DISIDA) on single-photon emission computed tomography analysis showed that both liver uptake and excretion times of DISIDA were significantly delayed in LPS/D-GalN-treated animals and were effectively recovered by DET and silymarin treatment. This report demonstrates that DET functions in the modulating multiple molecular targets or signaling pathways that counteract inflammation during the progression of fulminant hepatitis and may serve as a novel lead compound for future development of anti-inflammatory or hepatoprotective agents.

Endotoxin- and D-galactosamine-induced liver injury improved by the administration of Lactobacillus, Bifidobacterium and blueberry.

BACKGROUND: D-galactosamine together with lipopolysaccharide can lead to a pronounced secretion by Kupffer cells of pro-inflammatory mediators, which have been shown to be early and important mediators of liver injury. Probiotics and dietary supplementation with fruit or vegetable extracts with high content of antioxidants, such as blueberry, could be beneficial in protecting against hepatotoxicity. AIMS: To investigate whether blueberry and probiotics could attenuate liver injury induced by D-galactosamine and lipopolysaccharide. SUBJECTS: Sprague-Dawley rats were used. METHODS: Six experimental groups: acute liver injury control and five groups of liver injury treated by blueberry alone or by each of the probiotics strains (Lactobacillus plantarum DSM 15313 and Bifidobacterium infantis DSM 15159) with and without blueberry. Samples were collected 24 h after induction for bacterial test, liver function test, short chain fatty acids, myeloperoxidase, cytokines, malondialdehyde and glutathione. RESULTS: Alanine aminotransferase levels decreased significantly in all groups compared to liver injury control and DSM 15313 groups. Bilirubin, liver TNF-alpha, myeloperoxidase and acetic acid in cecum content decreased significantly in all groups, while liver glutathione values increased significantly in all groups compared to liver injury control. Liver IL-1beta and bacterial translocation to the liver and mesenteric lymph nodes decreased significantly in all groups except B. infantis DSM 15159 group compared to the liver injury control. Enterobacteriaceae count in cecum decreased significantly in the groups with blueberry plus probiotics compared to the other groups. CONCLUSION: Blueberry and probiotics exert protective effects on acute liver injury. They reduce the hepatocytes injury, the inflammation and the pro-inflammatory cytokines, and improve the barrier functions and antioxidant activity.

High hepatic glutathione stores alleviate Fas-induced apoptosis in mice.

BACKGROUND/AIMS: The agonistic Jo2 anti-Fas antibody reproduces human fulminant hepatitis in mice. We tested the hypothesis that enhancing hepatic glutathione (GSH) stores may prevent Jo2-induced apoptosis. METHODS: We fed mice with a normal diet or a sulfur amino acid-enriched (SAA(+)) diet increasing hepatic GSH by 63%, and challenged these mice with Jo2. RESULTS: The SAA(+) diet markedly attenuated the Jo2-mediated decrease in hepatic GSH and the increase in the oxidized glutathione (GSSG)/GSH ratio in cytosol and mitochondria. The SAA(+) diet prevented protein kinase Czeta (PKCzeta) and p47(phox) phosphorylations, Yes activation, Fas-tyrosine phosphorylation, Bid truncation, Bax, and cytochrome c translocations, the mitochondrial membrane potential collapse, caspase activation, DNA fragmentation, hepatocyte apoptosis, and mouse lethality after Jo2 administration. The protective effect of the SAA(+) diet was abolished by a small dose of phorone decreasing hepatic GSH back to the levels observed in mice fed the normal diet. Conversely, administration of GSH monoethyl ester after Jo2 administration prevented hepatic GSH depletion and attenuated toxicity in mice fed with the normal diet. CONCLUSIONS: The SAA(+) diet preserves GSSG/GSH ratios, and prevents PKCzeta and p47(phox) phosphorylations, Yes activation, Fas-tyrosine phosphorylation, mitochondrial permeabilization, and hepatic apoptosis after Fas stimulation. GSH monoethyl ester is also protective, suggesting possible clinical applications.