Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (c glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD 1 water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet 1 water). In comparison, HFD 1 coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor a (TNF-a), tissue transglutaminase, and transforming growth factor b and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor a in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-a and interferon-c and increased anti-inflammatory interleukin-4 and interleukin-10. Conclusion: Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid b-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation. (HEPATOLOGY 2010;52:1652-1661 N onalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and is associated with its clinical features, including visceral obesity, dislipidemia, and type 2 diabetes.1 NAFLD has high prevalence in the general population, and it can evolve into nonalcoholic steatohepatitis (NASH), cirrhosis, and complications such as liver failure and hepatocellular carcinoma. 2,3 A model in which rats without genetic modifications are given a high-fat, high-calorie diet is the gold standard for studying the pathogenetic factors involved in NASH. 4 NASH is a chronic inflammatory state in which ROS and several immunomodulatory factors contribute to liver injury. It is well documented that many natural substances, such as common foods and Abbreviations: adipo-R2, adiponectin receptor

The aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42–80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35–77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance.ConclusionsBreath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.

Inflammatory bowel diseases are associated with increased risk of developing colitis‐associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω‐3 polyunsaturated fatty acids (ω‐3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid‐free fatty acid (EPA‐FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA‐FFA are unknown in CAC. We tested the effectiveness of substituting EPA‐FFA, for other dietary fats, in preventing inflammation and cancer in the AOM‐DSS model of CAC. The AOM‐DSS protocols were designed to evaluate the effect of EPA‐FFA on both initiation and promotion of carcinogenesis. We found that EPA‐FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA–FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β‐catenin expression, whilst it increased apoptosis. In both arms, EPA‐FFA treatment led to increased membrane switch from ω‐6 to ω‐3 PUFAs and a concomitant reduction in PGE2 production. We observed no significant changes in intestinal inflammation between EPA‐FFA treated arms and AOM‐DSS controls. Importantly, we found that EPA‐FFA treatment restored the loss of Notch signaling found in the AOM‐DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA‐FFA is an excellent candidate for CRC chemoprevention in CAC.

Aspirin causes gastroduodenal ulcers and complications. Food bioactive compounds could exert beneficial effects in the gastrointestinal tract. We evaluated whether apple polyphenol extract (APE) reduced aspirin-induced injury to the rat gastric mucosa. Rats were treated with APE (10 24 M catechin equivalent) before oral aspirin (200 mg/kg). Cyclo-oxygenase-2 (COX-2), transforming growth factor-a (TGFa) and heparinbinding epidermal-growth-factor-like growth factor (HB-EGF) mRNA and protein expression were assessed by RT-PCR and Western blot analysis, respectively; malondialdehyde (MDA) was determined by HPLC; gastric secretion was evaluated in pylorus-ligated rats. APE decreased acute and chronic aspirin injury both macroscopically and microscopically (approximately 50 % decrease in lesion score; P,0·05). Aspirin up-regulated mRNA and protein expression of COX-2 and HB-EGF, but not of TGFa; APE reduced aspirin-induced mRNA and protein overexpression of COX-2 and HB-EGF; aspirin significantly increased gastric MDA and this effect was counteracted by APE pre-treatment. APE did not significantly affect gastric acid secretion. In conclusion, APE reduces aspirin-induced gastric injury independently of acid inhibition. We speculate that APE might be of therapeutic use in the prophylaxis of aspirin-related gastropathy. Apple polyphenols: Aspirin: Gastric injuryNon-steroidal anti-inflammatory drugs (NSAID), including aspirin, are among the most commonly used medications in the world. Gastrointestinal (GI) morbidities represent the most common adverse effects associated with NSAID use, with serious GI tract complications occurring in 1-4 % of NSAID users annually (1) . In particular, symptomatic or complicated ulcers are the most serious GI side effects. Low-dose aspirin (i.e. ,325 mg/d) increases the risk for GI bleeding and hospitalisation and an increasing amount of literature suggests that even cardiovascular doses of aspirin increase GI risk two to four times (2)