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Purpose: Troxerutin (TXER), a trihydroxyethylated derivative of the natural bioflavonoid rutin, abundantly found in tea, various fruits and vegetables, is known to exhibit ample pharmacological properties. In the present investigation, we examined the antineoplastic, therapeutic efficacy and furthermore the possible mechanisms of action of TXER against NAFLD/NASH progression to hepatocarcinogenesis. Methods: The effect of TXER (12.5, 25 or 50 mg/kg b.w/day) was evaluated on the nitrosodiethylamine (NDEA) model of hepatocarcinogenesis in rats, after 16 weeks of oral treatment, with special focus on liver specific enzymes, xenobiotic metabolizing enzymes, antioxidant status, lipid peroxidation profile, DNA damage, fibrosis, cell proliferation and inflammatory status. Results: Administration of TXER to hepatocellular carcinoma-bearing rats restored the enzyme activities and the hepatic architecture. Furthermore, TXER significantly curtailed NDEA-induced DNA damage, cell proliferation, inflammation, fibrosis and hepatic hyperplasia. Conclusion: This study provides the evidence that troxerutin exerts a significant therapeutic effect against liver cancer by modulating liver function enzymes, xenobiotic enzymes, oxidative damage, inhibiting cell proliferation, suppressing inflammatory response and induction of apoptosis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the effects of intrauterine growth retardation (IUGR) and Bacillus subtilis PB6 supplementation in formula milk (FORM) on growth performance, intestinal development and immune function of neonates using a porcine model. Methods: Fourteen pairs of normal birth weight and IUGR piglets (7 days old) were randomly assigned to receive FORM or FORM supplemented with B. subtilis PB6 (FORM-BsPB6) for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analysed for morphology, digestive enzyme activities, immune cell abundance, expression of genes associated with innate immunity and barrier function and microbial populations. Results: Regardless of diet, IUGR significantly decreased average daily dry matter intake and average daily weight gain ( P < 0.05). Moreover, IUGR significantly decreased plasma concentrations of immunoglobulin A, interleukin 1β, count and percentage of blood lymphocytes ( P < 0.05). Meanwhile, IUGR markedly decreased villous height and maltase activity, as well as mRNA abundance of Toll-like receptor 9 and Toll-interacting protein in the ileum ( P < 0.05). Regardless of body weight, FORM-BsPB6 markedly decreased the feed conversion ratio ( P < 0.05), due to better intestinal development, as indicated by increased villous height ( P < 0.05), activities of maltase and sucrase in the intestine ( P < 0.10). Moreover, both mRNA and protein abundances of zonula occludens-1 and claudin-1 in the ileum as well as the copy number of Bacillus in colonic digesta were increased ( P < 0.05) in piglets fed FORM-BsPB6 relative to FORM. Conclusion: The results of this study indicate that IUGR delayed growth, intestinal development and immune function of piglets, while FORM-BsPB6 improved digestive capability and intestinal barrier function. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of a diet containing fish oil (FD) during pregnancy and lactation in rats on the metabolic adaptations made by the offspring during early extrauterine life and to compare it to an olive oil diet (OD). Methods: Rats were mated and randomly allocated to OD or FD containing 10 % of the corresponding oil. During lactation, litters were adjusted to eight pups per dam. Fetuses of 20 days and pups of 0, 1, 10, 20 and 30 days of age were studied. Results: Body weight and length were lower in pups of the FD group from birth. The diet, milk, pups' plasma and liver of FD group had higher proportions of n-3 LCPUFA, but the content of arachidonic acid (ARA) was lower. Plasma glucose was higher, but unesterified fatty acids, triacylglycerols (TAG), 3-hydroxybutyrate and liver TAG in 1-day-old pups were lower in the FD group, and differences in some of these variables were also found in pups up to 30 days old. Liver lipoprotein lipase activity and mRNA expression, and the expression of carnitine palmitoyl transferase I, acyl-CoA oxidase and 3-hydroxy 3-methyl glutaryl-CoA synthase increased more at birth in pups of the FD group, but the expression of sterol regulatory element binding protein-1c and Δ6-desaturase mRNA was lower in the FD group. Conclusions: Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to test whether daily consumption of a beverage with high antioxidant power, combining extracts of green tea and apple over a period of 8 months, would affect blood and urinary concentrations of biomarkers of oxidative stress in Alzheimer's patients. Methods: The study included 100 subjects, 48 of them were Alzheimer's patients, aged 76.5 ± 3.5 years, and 52 were control subjects, aged 79 ± 4 years, without dementia. Three blood and urine samples were taken from each participant, the first ( T ) before starting the antioxidant or placebo beverage intake, the second ( T ) 4 months after the antioxidant or placebo beverage intake and the third ( T ) 8 months after the antioxidant or placebo beverage intake, and concentrations of biomarkers of oxidative stress were measured on serum, lysed erythrocytes or urine by UV-Vis spectrophotometry or by competitive in vitro enzyme-linked immunosorbent assay, according to the parameter analyzed. Results: The administration of the antioxidant beverage to the Alzheimer's patients prevented the decrease in total antioxidant status in the moderate phase of the disease ( T = 1.40 ± 0.10 mmol/L vs T = 1.20 ± 0.08 mmol/L), increased values of glutathione peroxidase and superoxide dismutase in initial (165 and 24 % respectively) and moderate phase (75 and 85 % respectively), and prevented the increase in protein carbonyls in moderate phase ( T = 0.17 ± 0.07 nmol/mg protein vs T = 0.21 ± 0.06 nmol/mg protein), with a significant decrease in protein carbonyls since the fourth month of the intake in initial phase ( T = 0.21 ± 0.06 nmol/mg protein vs T = 0.11 ± 0.05 nmol/mg protein). Conclusion: Our results suggest that antioxidant beverage could be used as a natural complementary therapy for alleviate or decrease the oxidative stress effects in the stages of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Purpose: Protein-restricted diet during pregnancy is related to oxidative stress and, as a consequence, damage to nephrogenesis. We investigated the effects of vinifera grape skin extract (ACH09)-derived polyphenols on preserving renal morphology of maternal protein-restricted 1-day-old offspring. Methods: Female C57/Bl-6 mice were fed two different isocaloric diets: control diet (19.3 % protein) and low-protein diet (6 % protein) with access to water or to the extract dissolved in drinking water (19.3 % protein plus ACH09 200 mg kg day and 6 % protein plus ACH09 200 mg kg day) throughout gestation. Renal morphology-glomerular number N[glom]; renal maturity-vascular glomeruli and avascular glomeruli ratio (v-N[glom]/a-N[glom]); medullar and cortical volumes, as well as mean glomerular volume, were analyzed in male offspring. Hepatic superoxide dismutase and catalase (CAT) activities were evaluated, and renal lipid peroxidation levels were measured. Results: Maternal protein restriction affected birth weight and naso-anal length in low-protein offspring compared to control and ACH09 restored both parameters. Protein restriction increased lipid peroxidation in kidney and liver and reduced CAT activity in low-protein group compared to control. Supplementation with ACH09 reduced the kidney oxidative damage and restored the antioxidant activity of CAT. ACH09 prevented glomerular loss and renal immaturity in the offspring. Conclusion: The treatment of low-protein-fed dams during pregnancy with ACH09 provides protection from early-life deleterious renal morphological changes. The protective effect of ACH09 may involve antioxidant action and vasodilator effect of the extract. [ABSTRACT FROM AUTHOR]

Purpose: The consequence of the increased demand due to the population expansion has put tremendous pressure on the natural supply of fruits. Hence, there is an unprecedented growing interest in the exploration of the potentials of underutilized fruits as alternatives to the commercially available fruits. Baccaurea angulata is an underutilized fruit widely distributed in Borneo Island of Malaysia. The present study was conducted to investigate the effects of B. angulata whole fruit (WF), skin (SK) and pulp (PL) juices on malondialdehyde (MDA) levels and antioxidant enzymes in rabbits fed high-cholesterol diet. Methods: Thirty-six male rabbits of New Zealand strain were randomly assigned to six groups. Rabbits were fed either a standard pellet (group NC) or a high-cholesterol diet (groups HC, PC, WF, SK and PL). Groups WF, SK and PL were also given 1 ml/kg/day B. angulata WF, SK and PL juices, respectively. Results: Baccaurea angulata had high antioxidant activities. The administration of the various juices significantly reduced ( p < 0.05) the concentration of induced plasma MDA. The decrease in the SOD, GPx, CAT and TAC levels caused by cholesterol feeding was also ameliorated with B. angulata. Conclusion: Our results show that B. angulata fruit is beneficial in positively influencing and managing oxidative damage. [ABSTRACT FROM AUTHOR]

Purpose: The beneficial effects of conjugated linoleic acid (CLA) mixture ( cis9, trans11, c9; trans10, cis12, t10) against gliadin-induced toxicity in HLA-DQ8-transgenic mice (DQ8) have been associated with improved duodenal cytoprotective mechanisms [nuclear factor-E2-related factor-2, Nrf2; acylpeptide hydrolase (APEH)/proteasome]. The present study was aimed at investigating the ability of individual CLA isomers to improve the efficacy of these defensive mechanisms and to protect against duodenal injury caused by the combined administration of gliadin and indomethacin (GI). Methods: Gluten-mediated enteropathy was induced in DQ8 mice by three intra-gastric administration of gliadin (20 mg kg/bw) and indomethacin (15 mg L) in drinking water for 10 days (GI). C9 or t10 CLA (520 mg kg/bw/day) were orally administered for 2 weeks. Pro-oxidant and toxic effects associated with GI treatment, anti-oxidant/detoxifying ability of c9 or t10-CLA and the protective effect induced by c9 pre-treatment (c9 + GI) were evaluated in DQ8 mice duodenum by combining enzymatic, immunoblotting, histological evaluation and quantitative real-time PCR assays. Results: GI treatment produces the time-dependent decline of the considered detoxifying mechanisms thus leading to pro-apoptotic and pro-oxidant effects. APEH/proteasome pathway was not markedly affected by individual CLA isomers, but duodenal redox status and activity/mRNA levels of Nrf2-activated enzymes were significantly improved by c9 administration. c9 pre-treatment protects against GI-mediated accumulation of oxidative stress markers, and histological examination reveals the increase of goblet cells number in mouse duodenum but induces only a partial recovery of APEH/proteasome activity. Conclusions: The activation of and adaptive response by low doses of c9 supplementation prevents distinct signs of gliadin-induced enteropathy in DQ8 mice. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we sought to find the effects and mechanisms of probiotic Lactobacillus casei Zhang ( L. casei Zhang) on the pro-inflammatory cytokine production and hepatic inflammatory response in a rat model of acute liver failure induced by lipopolysaccharide (LPS) and d-galactosamine (GalN). Methods: Male Wistar rats were orally administrated with or without L. casei Zhang for 30 days prior to challenge with LPS and GalN. Dexamethasone administrated group serving as a positive anti-inflammation control. Serum, intestinal and liver samples were collected 8 h after LPS/GalN challenge for histological, molecular and biochemical analysis. Results: LPS/GalN challenge alone resulted in significantly increased production of endotoxin, tumor necrosis factor- α (TNF- α), interleukin-1 beta (IL-1 β) and nitric oxide as compared to the normal control rats. Pretreatment with L. casei Zhang not only reduced these changes, but also attenuated hepatic inflammation as shown by improved histological assessment, decreased myeloperoxidase activity and reduced expression of IL-1 β and inducible nitric oxide synthase in the liver. L. casei Zhang supplementation significantly inhibited LPS/GalN-triggered phosphorylation of ERK, JNK and p-38 MAPK, but increased the expression of TLR2, TLR9 and PPAR-γ. Moreover, L. casei Zhang treatment prevented intestinal injury and modulated the intestinal ecology by increasing the fecal Lactobacillus and Bifidobacterium levels. Conclusions: Probiotic L. casei Zhang reduces LPS/GalN-induced pro-inflammatory cytokine and hepatic inflammation through modulating the TLR-MAPK-PPAR-γ signaling pathways and intestinal microbiota. [ABSTRACT FROM AUTHOR]

Purpose: Although amino acids (AA) are required for growth, little is known about the effect of a deficient AA supply on the composition and the contractile and metabolic properties of skeletal muscles. Methods: Protein metabolism, oxidative catabolism, glutathione system, and fiber-type composition of the longissimus (LM), rhomboideus (RM), and semitendinous (SM) muscles were compared between 42-day-old piglets pair-fed for 10 days either with a diet with a 28 % deficient supply of total sulfur AA (TSAA−) or with a diet with a sufficient supply of total sulfur AA (TSAA+). Results: The relative weight, protein mass, and protein synthesis of LM were 10-32 % lower in TSAA− pigs compared with TSAA+ pigs, while RM and SM were not affected by the TSAA supply. The TSAA supply affected the AA composition of muscles. Concentrations of Met and branched-chain AA were, respectively, 7 and 3 % lower in TSAA− pigs compared with TSAA+ pigs. The His concentration was 30 % higher in LM and SM in TSAA− pigs compared with TSAA+ pigs and unaffected in RM. The activity of citrate synthase was 14 % higher in all three muscles of TSAA− pigs. In these pigs, the β-hydroxy-acyl-CoA dehydrogenase activity was 20 % higher in RM compared with TSAA+ pigs while that of lactate dehydrogenase was 21 % lower in LM. Total and reduced glutathione concentrations were more than 70 % greater in RM than in LM or SM, and these concentrations were approximately 10 % lower in TSAA− pigs than in TSAA+ pigs. Conclusions: Results of this study indicate that a TSAA deficiency affects muscle properties in a muscle-dependent manner increasing the oxidative capacity of RM and reducing growth and glycolytic metabolism of LM. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze whether the combination of resveratrol and quercetin showed additive or synergic effects on body fat accumulation and triacylglycerol metabolism in adipose tissue from rats fed an obesogenic diet. Methods: Rats were divided into four dietary groups: a control group and three groups each treated with either resveratrol (15 mg/kg/day; RSV), quercetin (30 mg/kg/day; Q), or both (15 mg resveratrol/kg/day and 30 mg quercetin/kg/day; RSV + Q) for 6 weeks. White adipose tissues from several anatomical locations were dissected. Serum parameters were analyzed by using commercial kits. The activities of fatty acid synthase and heparin-releasable lipoprotein lipase (HR-LPL) were measured using spectrophotometric and fluorimetric methods, and protein expression of acetyl-CoA carboxylase (ACC), adipose tissue triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) by western blot. Results: The administration of either resveratrol or quercetin separately did not induce significant reductions in adipose tissue weights. By contrast, the combination of both molecules led to a significant reduction in all the fat depots analyzed. The percentage of reduction in each tissue was greater than the calculated additive effect. HR-LPL activity was reduced in RSV and RSV + Q groups. The activity of HSL was not modified. By contrast, ACC was inhibited and ATGL increased only by the combination of both polyphenols. Conclusion: The results obtained demonstrate a synergistic effect between resveratrol and quercetin and suggest that when these molecules are combined, a great number of metabolic pathways involved in adipose tissue triacylglycerol accumulation are affected. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the effects of neonatal malnutrition on the microbicidal response and viability of in vitro macrophages infected with Staphylococcus aureus sensitive/resistant to methicillin. Methods: Male Wistar rats ( n = 24) were divided into two distinct groups: nourished (rats breast-fed by mothers undergoing diet with 17 % casein) and malnourished (rats breast-fed by mothers undergoing diet with 8 % casein). Macrophages were recovered after surgical tracheostomy procedure by collecting bronchoalveolar lavage. Four systems were established: negative control, composed only by phagocytes; positive control, macrophages plus lipopolysaccharide; and two test systems, macrophages plus Staphylococcus aureus sensitive and resistant to methicillin. Plates were incubated at 37 °C for 24 h. After this period, tests for the analysis of cell viability and microbicidal response were performed. In the statistical analysis, the Student's t and ANOVA tests were used, accepting p < 0.05. Results: The neonatal malnutrition impaired the animals' body weight. There was a lower expression of the inducible nitric oxide enzyme (iNOS), nitric oxide production, and viability of macrophages infected with methicillin-resistant Staphylococcus aureus. However, increased production of superoxide anion in the malnourished group was detected. Conclusion: Neonatal malnutrition focusing on critical periods of development promoted lower expression of iNOS, nitric oxide production, cell viability, and exacerbated reactive oxygen species production. The high levels of reactive oxygen species may favor the onset of serious and systemic infections with fatal outcome if associated with methicillin-resistant Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Purpose: Several species of rodents are used to investigate the metabolism of quercetin in vivo. However, it is unclear whether they are a proper animal model. Thus, we compared the metabolism of quercetin in Wistar rats (rats), Balb/c mice (mice) and Mongolian gerbils (gerbils). Methods: We determined the levels of quercetin metabolites, quercetin-3-glucuronide (Q3G), quercetin-3′-sulfate (Q3′S) and methyl-quercetin isorhamnetin (IH), in the plasma, lungs and livers of three species of animals by high-performance liquid chromatography after acute and/or chronic quercetin administration. The metabolic enzyme activities in the intestinal mucosal membrane and liver were also investigated. Results: First, we found that after acute quercetin administration, the Q3′S level was the highest in gerbils. However, after long-term supplementation (20 weeks), Q3G was the dominant metabolite in the plasma, lungs and livers followed by IH and Q3′S in all animals, although the gerbils still had a higher Q3′S conversion ratio. The average concentrations of total quercetin concentration in the plasma of gerbils were the highest in both short- and long-term studies. The activities of uridine 5′-diphosphate-glucuronosyltransferase, phenolsulfotransferase and catechol-O-methyltransferase were induced by quercetin in a dose- and tissue-dependent manner in all animals. Conclusions: Taken together, in general, after long-term supplementation the metabolism of quercetin is similar in all animals and is comparable to that of humans. However, the accumulation of quercetin and Q3′S conversion ratio in gerbils are higher than those in the other animals. [ABSTRACT FROM AUTHOR]

Purpose: Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Methods: Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4 % w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. Results: DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. Conclusions: These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development. [ABSTRACT FROM AUTHOR]

Purpose: We have previously shown that quercetin modulates the proinflammatory effect of β-carotene (BC) induced by oral benzo[a]pyren (Bap) partly through the regulation of the JNK pathway. In the present study, we determined whether the combination of BC and quercetin regulates the antioxidant enzymes and the activation of NF-κB in Mongolian gerbils exposed to Bap. We also compared the combined effects of BC+ quercetin with that of BC+ ascorbic acid (C)+ α-tocopherol (E). Methods: The gerbils were given BC (10 mg/kg) alone or in combination with quercetin (50 or 100 mg/kg) or C (13 mg/kg)+E (92 mg/kg) by gavage 3 times/week for 6 months. During the first 2 months, the gerbils were exposed to Bap by intratracheal instillation once/week. The levels of proinflammatory cytokines, thiobarbituric acid reactive substances, antioxidant enzymes and NF-κB activation in the plasma or the lungs were determined. Results: Bap increased the level of proinflammatory cytokines and oxidative stress in the plasma or lungs, while it decreased the antioxidant systems. Bap also increased nuclear NF-κB levels in the lungs. BC partly recovered the Bap-induced decrease in antioxidant activity, antioxidant enzyme activities and glutathione levels but had no effect on proinflammatory cytokines and NF-κB translocation. BC in combination with quercetin or C+E suppressed all the harmful effects induced by Bap. All the effects of quercetin at 100 mg/kg were similar to the effect of C+E. Conclusion: BC in combination with quercetin or C+E rather than BC alone similarly suppresses the Bap-induced inflammatory reaction that was accompanied by the regulation of antioxidant enzymes and the translocation of NF-κB in vivo. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the hypoglycemic and antioxidant effects of shrimp astaxanthin on the kidney of alloxan-induced diabetic rats. Methods: Animals were distributed into four groups of six rats each: a control group (C), a diabetic group (D), a diabetic group supplemented with Astaxanthin (D+As) dissolved in olive oil and a diabetic group supplemented with olive oil (D+OO). In vitro antidiabetic effect was tested in plasma and kidney tissue. Results: The group D of rats showed significant ( P < 0.05) increase of glycemia, creatinine, urea and uric acid levels compared to those of the control group (C). Moreover, plasma and kidney malondialdehyde (MDA) and protein carbonyl (PCO) levels for the rats of the group D were significantly increased compared to the control group. Contrariwise, antioxidant enzyme activities, such as catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and non-enzymatic levels of reduced glutathione, were significantly ( P < 0.05) decreased in the plasma and kidney of diabetic rats compared to the control ones. The astaxanthin supplementation in rats diet improved the antioxidant enzyme activities and significantly decreased the MDA and PCO levels compared to diabetic rats. Indeed, no significant ( P ≥ 0.05) improvement was observed for the fourth group (D+OO) compared to the control group (C). Histological analysis of kidney showed glomerular hypertrophy and tubular dilatation for the diabetic rats. For D+As rats, these histopathological changes were less prominent. Conclusions: Our results suggest that shrimp astaxanthin may play an important role in reduction of oxidative damage and could prevent pathological changes in diabetic rats suggesting promising application of shrimp astaxanthin in diabet treatment. [ABSTRACT FROM AUTHOR]

Purpose: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. We aimed to clarify the impact of dietary walnut oil versus animal fat on hepatic steatosis, representing the initial step of multistage pathogenesis of NAFLD, in Zucker obese rats. Methods: Zucker lean ad libitum (a.l.), Zucker obese a.l. or Zucker obese pair fed (p.f.) to the lean received isocaloric diets containing 8 % walnut oil (W8), W14 or 14 % lard (L14) ( n = 10/group). Body weight, clinical serology, liver weight, lipid content and fatty acid composition and hepatic lipid metabolism-related transcripts were evaluated. Results: Compared to lean, Zucker obese a.l. and p.f. showed hepatic triacylglyceride (TAG) accumulation. In Zucker obese p.f., W14 compared to W8 and L14 reduced liver lipids, TAG as well as hepatic omega-6 (n-6)/n-3 ratio and SCD activity index [(C18:0 + C18:1)/C18:0 ratio] paralleled by decreased lipoprotein lipase mRNA in obese p.f. and elevated microsomal triglyceride transfer protein mRNA in lean and obese. Further, W14 elevated the fasting blood TAG and reduced cholesterol levels in obese. Conclusions: In our model, consumption of W14 inhibited hepatic lipid accumulation along with modulated hepatic gene expression implicated in hepatic fatty acid influx or lipoprotein assembly. These results provide first indication that dietary lipids from walnut oil are modulators of hepatic steatosis as the initial step of progressive NAFLD pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation is a hallmark of many diseases, such as atherosclerosis, autoimmune diseases, obesity, and cancer. Isoflavone-free soy protein diet (SPI) has been shown to reduce atherosclerotic lesions in a hyperlipidemic mouse model compared to casein (CAS)-fed mice, despite unchanged serum lipid levels. However, possible mechanisms contributing to the athero-protective effect of soy protein remain unknown. Therefore, we investigated whether and how SPI diet inhibits inflammatory responses associated with atherosclerosis. Methods: Apolipoprotein E knockout (apoE−/−) mice (5-week) were fed CAS or SPI diet for 1 or 5 week to determine LPS- and hyperlipidemia-induced acute and chronic inflammatory responses, respectively. Expression of NF-κB-dependent inflammation mediators such as VCAM-1, TNF-α, and MCP-1 were determined in aorta and liver. NF-κB, MAP kinase, and AKT activation was determined to address mechanisms contributing to the anti-inflammatory properties of soy protein/peptides. Results: Isoflavone-free soy protein diet significantly reduced LPS-induced VCAM-1 mRNA and protein expression in aorta compared to CAS-fed mice. Reduced VCAM-1 expression in SPI-fed mice also paralleled attenuated monocyte adhesion to vascular endothelium, a critical and primary processes during inflammation. Notably, VCAM-1 mRNA and protein expression in lesion-prone aortic arch was significantly reduced in apoE−/− mice fed SPI for 5 weeks compared with CAS-fed mice. Moreover, dietary SPI potently inhibited LPS-induced NF-κB activation and the subsequent upregulation of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, and MCP-1. Interestingly, SPI inhibited NF-κB-dependent inflammatory responses by targeting I-κB phosphorylation and AKT activation with no effect on MAP kinase pathway. Of the five putative soy peptides, four of the soy peptides inhibited LPS-induced VCAM-1, IL-6, IL-8, and MCP-1 protein expression in human vascular endothelial cells in vitro. Conclusions: Collectively, our findings suggest that anti-inflammatory properties of component(s) of soy protein/peptides may be a possible mechanism for the prevention of chronic inflammatory diseases such as atherosclerosis. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the preventive and therapeutic effects of Lactobacillus casei Zhang on impaired glucose tolerance (IGT) by using fructose-induced hyperinsulinemia rats. Methods: Rats were fed 25 % fructose solution for hyperinsulinemia with L. casei Zhang for prevention or therapy. Serum levels of insulin, glucagon-like peptide-2 (GLP-2), osteocalcin, malondialdehyde (MDA), total intestinal bile acids and hepatic glycogen contents were determined by assay kits. The major bacteria from feces and liver expression of adiponectin receptor 2 (AdipoR2), liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ) and vitamin K epoxide reductase complex subunit 1 mRNA were assessed by RT-PCR. Pancreas injury was evaluated by histological analysis. Results: Lactobacillus casei Zhang significantly increased numbers of Lactobacillus and Bifidobacterium and decreased Clostridium in the intestine ( p < 0.01). Meanwhile, liver glycogen contents were significantly decreased ( p < 0.05). In preventive group, accompanied by significantly lower insulin and GLP-2 levels ( p < 0.05), L. casei Zhang prevented rats from an increase in oral glucose tolerance area under curve (AUC) which was significant in hyperinsulinemia group ( p < 0.05). In therapeutic group, L. casei Zhang administration possessed improved glucose tolerance ( p < 0.05), which were associated with increased osteocalcin level ( p < 0.01), improved intestinal bile acids secretion ( p = 0.060), decreased serum MDA levels ( p < 0.05) and upregulation of LXR-α, PPAR-γ and AdipoR2 gene expression, as well as an increase in Bacteroides fragilis ( p < 0.05). Conclusions: Lactobacillus casei Zhang administration exert both preventive and ameliorative effect on oral glucose tolerance AUC in IGT rats but may be via different mechanisms. L. casei Zhang could prevent rats from increased AUC through GLP-2 lowering, while the ameliorative effect in high-fructose-fed post-adolescent rats may be via B. fragilis enriched vitamin K2-dependent osteocalcin mechanism in which AdipoR2, LXR-α and PPAR-γ signaling were involved. [ABSTRACT FROM AUTHOR]

Purpose: Tryptophan is an essential amino acid, precursor of serotonin. Serotonin (5HT) regulates the secretion of pituitary growth hormone (GH), which in turn stimulates the liver to produce insulin-like growth factor-I (IGF-I) that is necessary for development and growth. The aim of our study was to investigate the effects of an excess of tryptophan in the diet of pregnant rats on the differentiation of skeletal muscle tissue. Methods: We conducted an immunohistochemical study on the IGF-I expression in hepatic and muscle tissues in offspring, and then, we associated this molecular data with morphological effects on the structure of the muscle fibers and hepatic tissue at different postnatal weeks, from birth to sexual maturity. Measurements of 5HT, GH in blood, and of tryptophan hydroxylase (Tph) activity in gastrointestinal tracts tissue were also taken. Results: Hyperserotonemia and higher values of Tph activity were detected in both pregnant rats and pups. Very low levels of GH were detected in experimental pups. Morphological alterations of the muscle fibers and lower IGF-I expression in hepatic and muscle tissue in pups were found. Conclusions: Our data suggest that an excess of tryptophan in the diet causes hyperserotonemia in fetus. Hyperserotonemia results in an excess of serotonin in the brain where it has an adverse effect on the development of serotonergic neurons. The affected neurons do not regulate optimally the secretion of pituitary GH that consequently decreases. This limits stimulation in the liver to produce IGF-I, crucial for development and growth of pups. [ABSTRACT FROM AUTHOR]

Purpose: The beneficial effects of a seafood-rich diet are highly documented and can be attributed to both n-3 polyunsaturated fatty acids and other less studied nutritional components including protein and antioxidants. The aim of the work was to investigate whether an under-utilized seafood source, eggs (roe) and sperm (milt) from herring ( Clupea harengus), can affect lipid metabolism and inflammation in a mouse model transgenic for human tumor necrosis factor alpha (hTNFα). Methods: A high-fat control diet (25% total fats, 20% protein, w/w) or high-fat diets supplemented with herring roe (3.7% fat, 15% protein, w/w), or milt (1.3% fat, 15% protein) were administered to female C57BL/6 hTNFα mice. After 2 weeks, hepatic enzyme activity, gene expression, lipid and fatty acid composition, fatty acid composition of epididymal adipose tissue, and plasma lipid and cytokine levels were determined. Results: Animals fed herring roe and milt displayed an increased hepatic fatty acid β-oxidation and reduced fatty acid synthase activity. However, while plasma TAG was reduced, hepatic TAG and plasma and hepatic cholesterol levels were increased by the herring diets. Both herring diets led to a substantial shift in the n-6: n-3 ratio in both liver and ovarian white adipose tissue. The herring diets also increased plasma carnitine and reduced the carnitine precursor trimethyllysine. Plasma short-chained acylcarnitine esters were significantly increased, which may reflect an increased β-oxidation of long-chained fatty acids. In addition, the diets tended to reduce the plasma levels of pro-inflammatory cytokines. Conclusion: Herring roe or milt diets enhanced lipid catabolism and influenced the chronic inflammatory state in hTNFα-transgenic mice. [ABSTRACT FROM AUTHOR]

Purpose: To study the gluten metabolism in healthy individuals and its effect over the intestinal microbial activity. Methods: The faeces of eleven healthy subjects were analysed under 4 diet regimens: their normal gluten diet, a strict gluten-free diet (GFD), a GFD with a supplemental intake of 9 g gluten/day and a GFD with a supplemental intake of 30 g gluten/day. Gluten content, faecal tryptic activity (FTA), short-chain fatty acids (SCFAs) and faecal glutenasic activity (FGA) were analysed in faecal samples. Results: Faecal gluten contents, FTA, SCFAs and FGA varied significantly with different levels of gluten intake in the diet. When high gluten doses (30 g/day) were administered in the diet, SCFA concentrations (70.5 mmoles/kg faeces) were significantly different from those from the GFD period (33.8 mmoles/kg faeces) of the experiment. However, the FTA showed significant differences between the GFD (34 units) and the normal gluten-containing diet (60 units) and also between the GFD and the GFD + 30 g of gluten/day (67 units). When gluten was present in the diet, gluten was detected in the faeces, showing that at least a portion of the gluten ingested is eliminated in the large intestine, providing a substrate for intestinal microbial proteases. We have also shown the presence of faecal glutenasic activity that increased proportionally with the gluten intake in the diet, showing an enzymatic activity of 993 units in DSG, 2,063 units in DSG + 9 g and 6,090 units in DSG + 30 g. Conclusions: The activity of the intestinal microbiota is modified by gluten intake in the diet. The incorporation of gluten in the diet increases the activity of a gluten proteolytic activity in the faeces. [ABSTRACT FROM AUTHOR]

Purpose: Creatine belongs to a buffering system of cellular ATP level and has been reported to display direct antioxidant activity. Aim of this work was to investigate whether creatine treatment could ameliorate the antioxidant response of intestinal cells and limit the oxidative injury induced by anoxia and subsequent reoxygenation. Methods: Jejunal and ileal tracts of rat intestine were everted and incubated in vitro under normoxic, anoxic and reoxygenation conditions in the absence and in the presence of 10 mM creatine. (Na, K)-ATPase, γ-GT and antioxidant enzymes activities were determined in mucosal homogenate, as well as malondialdehyde production and HSP70 expression. Results: Both in jejunum and ileum, creatine treatment increases (Na, K)-ATPase activity; γ-GT is unaffected in jejunum but stimulated in ileum. In both tissues, creatine does not alter the antioxidant activities or malondialdehyde level. HSP70 expression is increased only in jejunum. Anoxic conditions stimulate antioxidant activities to a greater extent in jejunum compared to ileum; reoxygenation does not evoke further effects, but enhances malondialdehyde production in both tracts. The protective action of creatine, in reoxygenation, is more marked in jejunum as for its stimulation of antioxidant activities; however, in jejunum, a prooxidant action of creatine is suggested, since malondialdehyde production is enhanced by its presence; on the contrary in ileum, where HSP70 is overexpressed in reoxygenation, peroxidation level is significantly reduced. Conclusions: The presence of creatine seems to potentiate the defensive response of both tissues, in jejunum by means of cell antioxidant equipment, in ileum by the involvement of HSP70. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the effect of CLA supplementation on antioxidant metabolism in healthy overweight/obese Korean individuals. Methods: We performed a randomized, double-blind, placebo-controlled trial, where 29 healthy overweight/obese (BMI ≥ 23 kg/m) participants (2 men and 27 women) were randomly selected to receive placebo ( n = 15, 2.4 g olive oil/day) or 2.4 g/day CLA mixture ( n = 14, 36.9% of cis-9, trans-11 and 37.9% of trans-10, cis-12) for 8 weeks. Results: There were no significant differences in plasma total radical-trapping antioxidant potential (TRAP), lipid peroxidation (conjugated dienes), lipid-soluble antioxidant vitamin concentration, erythrocyte antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase) activities, and leukocyte DNA damage between the CLA and placebo groups. Conclusions: The data suggest that short-term supplementation (8 weeks) with CLA (2.4 g/day) might have no significant effects on lipid peroxidation and antioxidant metabolism. [ABSTRACT FROM AUTHOR]

Background: The role of iron (Fe) in bone formation and disease have not received much attention, a fact that is interesting given the known biochemical role that this mineral has upon collagen maturation together with the high prevalence of Fe-deficiency anaemia worldwide. Aim: To investigate the changes in bone formation, resorption and mineral content in developing rats with induced nutritional Fe-deficiency anaemia. Methods: Thirty male Wistar rats were divided into two groups, a control group receiving AIN-93G diet with normal-Fe content and an anaemic group receiving AIN-93G diet with low-Fe content for 40 days. Both diets were prepared with an adequate calcium (Ca) and phosphorus (P) content. The most representative serum bone turnover biomarkers and femur and sternum calcium and phosphorus content, together with sternum Fe content were determined in both experimental groups. Results: In anaemic rats, bone matrix formation diminished as revealed by the lower amount of procollagen type I N-terminal propeptide. Bone resorption process increased in Fe deficiency as shown by the increase of serum parathyroid hormone, tartrate-resistant acid phosphatase and levels of degradation products from C-terminal telopeptides of type I collagen released to the serum. In addition, mineralization process was affected by Fe deficiency, because Ca and P content in femur decreased markedly. Conclusions: Fe-deficiency anaemia had a significant impact upon bone, affecting bone mineralization, decreasing the matrix formation and increasing bone resorption, therefore it is of great interest to assess bone status in situation of Fe-deficiency anaemia. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common and preventable cancers. Regular consumption of apples is conducive to reduction in CRC risk. Aim of the study: To evaluate effects of modified apple polysaccharide (MAP) on tumorigenesis in a mouse model of colitis-associated colon cancer. Methods: One hundred male ICR mice were administered with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Forty mice were given no further treatment, the rest were fed basal diet blended with three different doses of MAP; 2.5, 5, and 10% (20 mice in each group). Results: MAP significantly protected ICR mice against DMH/DSS-induced tumorigenesis. The incidence of tumor development was 90% (18/20) in the mice treated with DMH/DSS, but that was reduced to 25% (5/20), 15% (3/20), and 5% (1/20), respectively, in the mice treated with basal diets plus 2.5, 5, and 10% of MAP. Study of apoptosis of colonic epithelial cells revealed that MAP moderately increased apoptosis, suggesting that the anti-tumor potency of MAP was probably attributed to its ability to induce apoptosis. Western blot analysis demonstrated that carbohydrate-binding protein galectin-3 changed in both the nucleus and the cytoplasm during the process from colitis to colon cancer in the model. And MAP could inhibit the binding of galectin-3 to its ligand: this is, at least in part, the possible mechanism of MAP by enhancing apoptosis and preventing tumorigenesis. Conclusions: These data suggest that MAP has a potential role in clinical prevention and treatment for colon cancer. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common etiologies of chronic liver disease worldwide. The pathogenesis of metabolic syndrome associated with NAFLD is still under debate. Aim of the scope: This study has investigated the hepatic biochemical and histological changes and also insulin resistance in metabolic syndrome associated with NAFLD. Methods: Young male Wistar rats fed a high-fat diet ( HFD 42.2% beef tallow) together with N-nitro- l-arginine methyl ester (L-NAME; 80 mg/L in drinking water) for 8 weeks and subsequently with 2% d-limonene for the final 4 weeks. Results: HFD-fed rats treated with L-NAME showed increased systolic blood pressure, heart rate, fasting blood glucose, plasma insulin, hepatic marker enzymes, hepatic lipids, circulatory lipid peroxidation by-products, and hepatic phase I enzyme activities with decreased circulatory nonenzymic antioxidant concentrations and hepatic phase II enzyme activities. Dietary supplementation with d-limonene reversed the HFD and L-NAME-induced changes and restored pathological alteration of liver and pancreas. Conclusions: These data provide new insights into the therapeutic approach of d-limonene against the development of the metabolic syndrome associated with NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: Oxidized fats are known to induce oxidative stress resulting in the up-regulation of antioxidant enzymes, with the underlying mechanism being unclear. It is known, however, that the response of tissues to oxidative stress is mediated by redox-sensitive transcription factors such as NF-κB and Nrf2. The aim of this study, therefore, was to test the hypothesis that ingestion of an oxidized fat causes activation of these transcription factors in the small intestinal mucosa. Methods: Female mice were randomly assigned to 2 groups of 12 mice each and administered orally by gavage either oxidized or fresh fat once per day. Results: After 6 days of treatment, mice were killed, intestinal mucosa was isolated, and nuclear concentration of NF-κB and Nrf2 and expression of NF-κB- and Nrf2-regulated oxidative stress-responsive genes were determined. Oxidized fat markedly increased nuclear concentration of NF-κB and Nrf2 and transcript levels of oxidative stress-responsive genes, like aldo-keto reductase 1B8, vanin-1, glutathione peroxidase 1, and superoxide dismutase-1. In addition, oxidized fat increased the concentrations of PPAR-regulated genes. Conclusions: The activation of oxidative stress-sensitive pathways likely reflects an adaptive response of the intestinal mucosa to prevent oxidative damage to the intestinal mucosa. [ABSTRACT FROM AUTHOR]

Background: The dietary flavanol (−)-epicatechin has been suggested to mediate its vasodilatory effect by increasing nitric oxide levels in endothelial cells. Aim of the study: To directly prove the formation of nitric oxide (NO) in human endothelial cells (HUVEC) in vitro by trapping NO to yield a fluorescent nitrosamine. Methods: HUVEC were treated with (−)-epicatechin; nitrite and NO formation were determined by reductive chemiluminescence detection and the NO-sensitive fluorophore 5-methoxy-2-(1 H-naphthol[2,3-d]imidazol-2-yl)-phenol copper complex (MNIP-Cu), respectively. MNIP was synthesized in a rapid and convenient one-step microwave reaction. Endothelial nitric oxide synthase (eNOS) mRNA levels and mRNA stability were measured. Results: Incubation with (−)-epicatechin (0.3-10 μM) led to elevated NO levels in HUVEC measured via reductive chemiluminescence detection and visualized as the fluorescent NO derivative of MNIP. Expression of eNOS mRNA and mRNA stability were not affected by (−)-epicatechin treatment within the time frame studied. Conclusion: (−)-Epicatechin augments the level of NO in endothelial cells, a process suggested to be responsible for the vasodilatory properties of the compound. [ABSTRACT FROM AUTHOR]

Background: Apples abundant in phenolic compounds show a variety of biological activities that may contribute to beneficial effects against some chronic diseases. Purpose: The aim of our study was to assess the protective effect of cloudy apple juice against chemical-induced oxidative stress in rats. Methods: Male Wistar rats were treated with apple juice per os, 10 mL/kg/day for 28 days and with a single dose of N-nitrosodiethylamine (NDEA), 150 mg/kg or carbon tetrachloride (CCl), 2 mL/kg, 24 h before killing. Two groups of rats not pretreated with juice were administered each of the xenobiotics alone. Results: Microsomal lipid peroxidation in the liver was decreased in rats pretreated with juice by 52-87% when compared to animals given NDEA or CCl alone. Pretreatment with juice protected antioxidant enzymes: catalase, glutathione peroxidase and glutathione reductase but not superoxide dismutase. Their activity was recovered by 49-173% when compared to that in rats given either toxicant alone. The plasma activity of paraoxonase1 was reduced by both toxicants and was increased by 23% in the apple/CCl group. A rise in plasma protein carbonyls caused by the xenobiotics was reduced by 20% only in apple/NDEA-treated rats. Also, in this group of animals, a 9% decrease in DNA damage in blood leukocytes was observed. Conclusion: Phytochemicals in commonly consumed apple juice may protect some macromolecules against oxidative insult induced by xenobiotics. [ABSTRACT FROM AUTHOR]