Ulcerative colitis results in differential metabolism of cranberry polyphenols by the colon microbiome in vitro.

The microbiome plays a major role in polyphenol metabolism, producing metabolites that are bioavailable and potentially more bioactive than the compounds from which they are derived. However, the microbiome can vary among individuals, and especially for those with co-morbidities, such as ulcerative colitis. In subjects with ulcerative colitis, the consequence of a 'dysbiotic' microbiome is characterized by decreased diversity of microbiota that may impact their capability to metabolize polyphenols into bioavailable metabolites. On this premise, the microbiome metabolism of cranberry polyphenols between healthy individuals and those with ulcerative colitis was compared in vitro. Fecal samples from volunteers, with or without diagnosed ulcerative colitis, were cultured anaerobically in the presence of cranberry polyphenols. The resulting metabolites were then quantified via LC-ESI-MS/MS. 16S rRNA metagenomics analysis was also utilized to assess differences in microbiota composition between healthy and ulcerative colitis microbiomes and the modulatory effects of cranberry polyphenols on microbiota composition. Healthy microbiomes produced higher (p < 0.05) concentrations of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone and 3-hydroxyphenylacetic acid in comparison to ulcerative colitis microbiomes. Additionally, healthy microbiomes contained a higher (p < 0.05) abundance of Ruminococcaceae, which could explain their ability to produce higher concentrations of cranberry polyphenol metabolites. Health status and the presence of cranberry polyphenols also significantly impacted the production of several short-chain and branched-chain fatty acids. These results suggest that efficiency of polyphenol metabolism is dependent on microbiota composition and future works should include metabolite data to account for inter-individual differences in polyphenol metabolism.

Açai pulp supplementation as a nutritional strategy to prevent oxidative damage, improve oxidative status, and modulate blood lactate of male cyclists.

PURPOSE: Açai pulp is a source of phytochemicals and has been associated with antioxidant, anti-inflammatory, and antigenotoxic effects. This study aimed to assess the effects of açai pulp consumption on oxidative, inflammatory, and aerobic capacity markers of cyclist athletes. RESEARCH METHODS AND PROCEDURES: A crossover, randomized, placebo-controlled, single-blind study was developed with ten male cyclists (33.5 ± 4.7 years old, body mass index of 23.9 ± 1.38 kg/m2, and training load around 1875 ± 238 AU/week). The athletes consumed 400 g/day of pasteurized açai pulp (AP) or placebo (PL) for 15 days, with a 30-day wash-out period between trials. Lipid peroxidation, serum antioxidant capacity, DNA damage in peripheral blood (Comet assay), IL-6 and TNF-alpha, blood lactate concentration during effort, anaerobic threshold intensity (ATi), maximum workload reached (Wmax), rating of perceived exertion threshold (RPET), and heart rate threshold (HRT) were evaluated before and after each intervention. Data were analyzed using a linear regression model with mixed effects (p ≤ 0.05). RESULTS: Increased serum antioxidant capacity (p = 0.006) and decreased lipid peroxidation (p = 0.01) were observed in subjects after intervention with AP. Blood lactate levels during effort significantly decreased (by 29%, p = 0.025) and ATi increased (p = 0.006) after AP. No significant effect on DNA damage was attributed to AP consumption. CONCLUSION: We found notable effects of AP intervention on antioxidant status in athletes. Both the reduction in blood lactate concentration and increase in ATi during the effort suggest an overall improvement in the aerobic capacity of the cyclists, confirming that AP consumption may influence variables associated with performance in endurance athletes.

Cocoplum (Chrysobalanus icaco L.) decreases doxorubicin-induced DNA damage and downregulates Gadd45a, Il-1ß, and Tnf-α in vivo.

DNA damage and inflammation are promising targets in disease prevention studies. Since these pathways have shown to be modulated by dietary components, investigating the molecular effects of food becomes relevant. This study aimed at investigating the protective effects of cocoplum (Chrysobalanus icaco L.) against doxorubicin (DXR)-induced damage. Rats were treated with cocoplum (100, 200 or 400mg/kg/day) for 14days, associated or not with DXR (15mg/kg b.w.). Tissue-targeted comet assay and the oxidative stress parameters oxidized/reduced glutathione and catalase were investigated in liver, kidney, and heart. The expressions of DNA damage/repair (Gadd45a, Parp1, Xrcc2) and proinflammatory genes (Il-1ß, Il-6, Nf-κb, Tnf-α) were performed by real-time quantitative PCR. Cocoplum decreased DNA damage and the expressions of Gadd45a, Il-1ß, and Tnf-α induced by DXR. These findings demonstrate that cocoplum fruits possess antigenotoxic and anti-inflammatory effects against DXR-induced damage and encourage other in vivo/clinical studies with this fruit.

Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver.

Some important environmental factors that influence the development of cardiovascular diseases (CVD) include tobacco, excess alcohol, and unhealthy diet. Methionine obtained from the diet participates in the synthesis of DNA, proteins, lipids and affects homocysteine levels, which is associated with the elevated risk for CVD development. Therefore, the aim of this study was to investigate the manner in which dietary methionine might affect cellular mechanisms underlying CVD occurrence. Swiss albino mice were fed either control (0.3% DL-methionine), methionine-supplemented (2% DL-methionine), or a methionine-deprived diet (0% DL-methionine) over a 10-week period. The parameters measured included plasma homocysteine concentrations, oxidative stress by reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, levels of inflammatory cytokines IL-1ß, TNF-α, and IL-6, as well as expression of genes associated with CVD. The levels of apolipoprotein A5 (APOA5), a regulator of plasma triglycerides, were measured. The methionine-supplemented diet increased oxidative stress by lowering the GSH/GSSG ratio in heart tissues and decreased expression of the genes Apob, Ctgf, Serpinb2, Spp1, Il1b, and Sell, but elevated expression of Thbs4, Tgfb2, Ccr1, and Vegfa. Methionine-deprived diet reduced expression of Col3a1, Cdh5, Fabp3, Bax, and Hbegf and increased expression of Sell, Ccl5, Itga2, Birc3, Msr1, Bcl2a1a, Il1r2, and Selp. Methionine-deprived diet exerted pro-inflammatory consequences as evidenced by elevated levels of cytokines IL-1ß, TNF-α, and IL-6 noted in liver. Methionine-supplemented diet increased hepatic IL-6 and cardiac TNF-α. Both methionine supplementation and deprivation lowered hepatic levels of APOA5. In conclusion, data demonstrated that a methionine-supplemented diet modulated important biological processes associated with high risk of CVD development.

Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model.

Deficiency of vitamin D3, a lipophilic micronutrient, plays a role in the development of some chronic diseases. Vitamin D3 deficiency affects 25-50% of the human population and has been associated with increased risk for development of hypertension. DNA damage induced by reactive oxygen species (ROS) occurs more often in hypertensive than in normotensive individuals, and vitamin D3 status can influence this relationship. The aim of this study was to evaluate whether a diet supplemented with (10,000 IU/kg) or deficient in (0 IU/kg) vitamin D3, compared to a vitamin D3 control diet (1000 IU/kg), would modulate DNA damage and ROS production in spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats after 12 weeks of treatment. ROS production was assessed by measuring the oxidative burst of neutrophils. DNA damage was evaluated using the comet assay in peripheral blood and the micronucleus test in bone marrow and peripheral blood. Vitamin D3 supplementation did not induce DNA damage and did not change neutrophil ROS production in SHR and WKY rats. Vitamin D3 deficiency induced neutrophil ROS production and a high frequency of micronucleus formation in the bone marrow and peripheral blood of SHR rats only, and induced DNA damage (comet) in peripheral blood of both SHR and WKY rats. In conclusion, vitamin D3 deficiency showed a more pronounced effect on hypertensive animals. Population studies are needed to test whether this relationship also exists in humans.

Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring.

SCOPE: Vitamin B6 plays crucial roles on brain development and its maternal deficiency impacts the gamma-aminobutyric acid (GABA)ergic, serotonergic, glutamatergic, and dopaminergic systems in offspring. However, the molecular mechanisms underlying these neurological changes are not well understood. Thus, we aimed at evaluating which components of those neurotransmitter metabolism and signaling pathways can be modulated by maternal vitamin B6 -deficient or B6 -supplementated diets in the hippocampus of rat dams and their offspring. METHODS AND RESULTS: Female Wistar rats were fed three different diets: control (6 mg vitamin B6 /kg), supplemented (30 mg vitamin B6 /kg) or deficient diet (0 mg vitamin B6 /kg), from 4 weeks before pregnancy through lactation. Newborn pups (10 days old) from rat dams fed vitamin B6 -deficient diet presented hyperhomocysteinemia and had a significant increase in mRNA levels of glutamate decarboxylase 1 (Gad1), fibroblast growth factor 2 (Fgf2), and glutamate-ammonia ligase (Glul), while glutaminase (Gls) and tryptophan hydroxylase 1 (Tph1) mRNAs were downregulated. Vitamin B6 supplementation or deficiency did not change hippocampal global DNA methylation. CONCLUSION: A maternal vitamin B6 -deficient diet affects the expression of genes related to GABA, glutamate, and serotonin metabolisms in offspring by regulating Gad1, Glul, Gls, and Tph1 mRNA expression.

Effects of maternal vitamin B6 deficiency and over-supplementation on DNA damage and oxidative stress in rat dams and their offspring.

Vitamin B6 is a cofactor for more than 140 essential enzymes and plays an important role in maternal health and fetal development. The goal of this study was to investigate the effects of maternal vitamin B6 on DNA damage and oxidative stress status in rat dams and their offspring. Female Wistar rats were randomly assigned to three dietary groups fed a standard diet (control diet), a diet supplemented with 30 mg/kg of vitamin B6, or a deficient diet (0 mg/kg of vitamin B6) for 10 weeks before and during mating, pregnancy and lactation. The dams were euthanized at weaning, and their male pups were euthanized either 10 days or 100 days after birth. We found that maternal vitamin B6 deficiency increased the micronucleus frequency in peripheral blood and bone marrow cells and also increased the concentration of hepatic TBARS (thiobarbituric acid reactive substances) in newborn pups (10 days old). In conclusion, maternal 5- to 6-fold over-supplementation of vitamin B6 had no adverse effects, however its deficiency may induce chromosomal damage and hepatic lipid peroxidation in the offspring.

Influence of Marolo (Annona crassiflora Mart.) pulp intake on the modulation of mutagenic/antimutagenic processes and its action on oxidative stress in vivo.

Brazilian savanna constitutes a valuable ecoregion that contributes to the supply of fruit known worldwide for its nutritional value and peculiar flavors. Among them, the Marolo (Annona crassiflora Mart.) fruit is known for its use in folk medicine. In order to establish the safety of Marolo for human consumption, this study evaluated the following: the chemical composition of Marolo pulp; its mutagenic and antimutagenic activities using micronucleus test; and the oxidative stress induced in the livers of mice fed a diet containing 1%, 10% or 20% pulp. It was observed that the chemical composition of marolo pulp was similar to that of common fruit; nevertheless, its lipidic content and energetic values were higher. In the mice fed experimental diets, the biochemical parameters of the blood serum showed normal levels of glucose, triglycerides, and cholesterol. The micronucleus test indicated neither mutagenic nor antimutagenic effects of Marolo consumption on bone marrow cells but showed potentialization of cyclophosphamide (CP). The oxidative stress levels observed indicated that CP was not exerting a great influence on the induction of reactive oxygen species. As the whole fruit is a complex matrix, the interactions between its components could be responsible for its negative and positive biological effects.