Effects of moderate ethanol exposure on risk factors for cardiovascular disease and colorectal cancer in adult Wistar rats.

While past studies have provided evidence linking excessive alcohol consumption to increased risk for cardiovascular diseases (CVDs) and colorectal cancer (CRC), existing data on the effects of moderate alcohol use on these conditions have produced mixed results. The purpose of this study was to investigate the effects of moderate alcohol consumption on risk factors associated with the development of CVDs and CRC in adult rats. Twenty-four, 14-month-old, non-deprived male Wistar rats were randomly assigned to either an ethanol group, which consisted of voluntary access to a 20% (v/v) ethanol solution on alternate days, or a water control group (n = 12/group) for 13 weeks. Blood samples were collected to analyze levels of albumin, glucose, adiponectin, lipids, oxidized low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apoA1), C-reactive protein (CRP), high-mobility group box 1 protein (HMGB-1), tumor necrosis factor-alpha (TNF-α), thyroxine, thyroid-stimulating hormone, 8-oxo-2'-deoxyguanosine (8-oxo-dG), liver function enzymes, and antioxidant capacity. Colonic gene expression related to colon carcinogenesis was also assessed. Ethanol-treated rats were found to have significantly higher HDL-C and apoA1 levels compared to controls. Moderate alcohol consumption led to significantly lower CRP levels and a trend for decrease in HMGB-1, TNF-α, and 8-oxo-dG levels. In the ethanol-exposed group, colonic gene expression of superoxide dismutase was upregulated while aldehyde dehydrogenase 2 showed a trend for increase compared to the control group. These results indicate that adopting a moderate approach to alcohol consumption could potentially improve health biomarkers related to CVD and CRC by increasing HDL-C levels and antioxidant activity and reducing DNA damage and inflammatory activity.

The effects of mango consumption on vascular health and immune function.

Objectives: Heart disease, caused by atherosclerosis, is the leading cause of death. Maintaining vascular integrity is crucial to reducing atherosclerosis risk. Mangos are rich in fiber, vitamins, minerals, and phytochemicals that may offer cardioprotective and immune-boosting benefits. However, their effects on the vasculature and immune system in adults with overweight and obesity remain unclear. The objective of this study was to investigate the effects of mango consumption on vascular health and immune function in adults with overweight and obesity. Methods: In a 12-week, crossover study, 27 overweight and obese participants consumed either 100 kcals of mangos daily or isocaloric low-fat cookies daily. Fasting blood samples were collected at baseline, week 4, and week 12 and analyzed for vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin, sCD4, sCD8, sCD3E, and sCD45, tumor necrosis factor-alpha (TNF-α), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Results: Mango consumption significantly decreased VCAM-1 between baseline and week 4 (P = 0.046) and week 12 (P = 0.004). CAT increased between baseline and week 12 (P = 0.035) with mango consumption. GPx increased at week 12 compared to baseline and week 4 (P < 0.05). At week 12, SOD was higher after mango consumption compared to low-fat cookie consumption (P = 0.046). There were no significant differences in ICAM-1, P-selectin, E-selectin, sCD4, sCD8, sCD3E, sCD45 or TNF-α concentrations (P > 0.05 for all non-significant results). Conclusions: This study suggests that 100 kcals of mangos may benefit the integrity of the vasculature by reducing VCAM-1 and increasing SOD, CAT, and GPx levels. Mangos can be an alternative snack for improving atherosclerosis and oxidative stress risk factors.

Dietary intake of pistachios or mixed nuts results in higher systemic antioxidant capacity with minimal effects on bone in adolescent male rats.

Nutrition is a key determinant of bone health and attainment of peak bone mass. Excess oxidative stress induces bone loss while increasing antioxidant capacity promotes protective effects on bone. Nuts are rich in antioxidants; therefore, we tested the hypothesis that compared to a control diet high in fat (40 % energy) and cholesterol, diets containing isocaloric amounts of pistachios (8·1 % g/g) or mixed nuts (7·5 % g/g) for 8 weeks would result in greater bone health in male adolescent (3 weeks; a state of continued skeletal growth) Sprague-Dawley rats. We found no difference in bone mechanical properties among groups. Tibial apparent density was ~5 % higher in the pistachio and mixed nuts groups v. control (P < 0·05) with no clear difference detected for the femur. Expressions of genes known to impact bone turnover and serum bone turnover biomarkers were unaffected by either diet relative to control. Serum antioxidant capacity was ~2-fold higher in the pistachio and mixed nuts groups compared with control (P < 0·05) but were similar between groups. Therefore, pistachios and mixed nuts may increase tibial density, in part, due to increasing antioxidant capacity. Longer dietary interventions may be necessary to elicit detectable changes in other bones (e.g. femur) and to detect potential mechanisms for the possible bone protective effects of nuts.

Effects of Mixed Nuts on Colonic Cell Proliferation and Ptgs2 and Rela Gene Expression.

BACKGROUND/AIM: Nut consumption is associated with lower risk of colorectal cancer (CRC). Previously, single nut varieties have been investigated but there is limited research on the consumption of a nut mixture and the underlying mechanisms. This study examined mixed nut consumption's effect on colonic cell proliferation, apoptosis, and gene expression involved in CRC. MATERIALS AND METHODS: Thirty 21-day old Sprague Dawley rats were divided into three groups: control (no nuts), pistachio or mixed nut for 8 weeks. Ki-67 quantitative immunostaining was used to mark proliferative cells and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptotic cells. Real-time quantitative polymerase chain reaction analysis was used to determine colonic gene expression of prostaglandin endoperoxide synthase 2 (Ptgs2), nuclear factor kappa-B p65 subunit (Rela), cyclin D1 (Ccnd1), peroxisome proliferator-activated receptor gamma (Pparg), O6-methylguanine-DNA-methyltransferase (Mgmt), 8-oxoguanine glycosylase (Ogg1), superoxide dismutase (Sod), and catalase (Cat). RESULTS: DNA damage, determined using 8-oxo-deoxyguanosin, was found to be lower in the mixed nut group only (p<0.05). Differences in proliferation and apoptosis among all three groups were not significant. Lower levels of the inflammatory marker, Ptgs2, were observed between the pistachio group and the control (p=0.035). The pistachio and mixed nut groups had lower levels of Rela compared to the control (p=0.029). Differences among diets for Ccnd1, Pparg, Mgmt, Ogg1, Sod, and Cat were not significant. CONCLUSION: Mixed nut consumption reduced DNA damage possibly via down-regulation of Rela inflammation gene expression without changes to colonic cell proliferation and apoptosis.

Fresh Mango Consumption Promotes Greater Satiety and Improves Postprandial Glucose and Insulin Responses in Healthy Overweight and Obese Adults.

Mangos are an understudied fruit rich in fiber and polyphenols that have been linked to better metabolic outcomes and promotion of satiety. The purpose of this study was to examine the effect of mango consumption on postprandial glucose, insulin, and satiety responses. Using a randomized crossover study design, 23 overweight and obese men and women consumed 100 kcal snacks of fresh mangos or isocaloric low-fat cookies on two separate occasions. Insulin and satiety hormones were measured at baseline and 45 min post-snack consumption. Glucose was measured at baseline, 30, 60, 90, and 120 min after snack consumption. Satiety questionnaires were completed at baseline and every 20 min for 120 min post-consumption. Both mangos and low-fat cookies increased insulin, with a significantly lower increase for mangos compared with low-fat cookies at 45 min post-snack consumption (P ≤ .05). Glucose increased at 30 min for both snacks; however, the increase was significantly higher for low-fat cookie consumption (P ≤ .05). Cholecystokinin increased after mangos and low-fat cookie consumption (P ≤ .05); however, no differences were detected between the snacks. Adiponectin increased after mango consumption (P ≤ .05) but not after low-fat cookies. Mango consumption reduced hunger, anticipated food consumption and thirst, and increased feelings of fullness (P ≤ .05). Low-fat cookie consumption increased fullness for a shorter time period and did not reduce participants' desire to eat. These results suggest that relative to a refined cookie snack, mangos promote greater satiety and improve postprandial glycemic responses. Future research on long-term effects of mango consumption on food intake, weight control, and glucose homeostasis is warranted. Clinical Trial Registration number: #NCT03957928.

Dried Plum Consumption Improves Total Cholesterol and Antioxidant Capacity and Reduces Inflammation in Healthy Postmenopausal Women.

Dried plums contain bioactive components that have demonstrated antioxidant and anti-inflammatory effects. The objective of this study was to determine if dried plum consumption reduces the risk factors for cardiovascular disease (CVD) in postmenopausal women, specifically examining lipid profiles, oxidative stress, antioxidant capacity, and inflammation in a dose-dependent manner. We conducted a 6-month, parallel-design controlled clinical trial, where 48 postmenopausal women were randomly assigned to consume 0, 50, or 100 g of dried plum each day. After 6 months of intervention, total cholesterol (TC) in the 100 g/day treatment group (P = .002) and high-density lipoprotein cholesterol in the 50 g/day treatment group (P = .005) improved significantly compared to baseline. Inflammatory biomarkers interleukin-6 (P = .044) and tumor necrosis factor-α (P = .040) were significantly lower after 6 months within the 50 g/day dried plum group compared to baseline. Moreover, total antioxidant capacity increased significantly within the 50 g/day group (P = .046), and superoxide dismutase activity increased significantly within both 50 and 100 g/day groups (P = .044 and P = .027, respectively) after 6 months compared to baseline. In addition, plasma activities of alanine transaminase (P = .046), lactate dehydrogenase (P = .039), and creatine kinase (P = .030) were significantly lower after 6 months in the 50 g/day dried plum group. These findings suggest that daily consumption of 50-100 g dried plum improves CVD risk factors in postmenopausal women as exhibited by lower TC, oxidative stress, and inflammatory markers with no clear dose dependence.

Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats.

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.

Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review.

Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as "vitamin D," "colitis," "inflammatory bowel disease," "inflammation," "apoptosis," "cell proliferation," and "gut bacteria". Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis.

Snack selection influences glucose metabolism, antioxidant capacity and cholesterol in healthy overweight adults: A randomized parallel arm trial.

Including carbohydrate/fructose-rich foods (predominantly fruit) in the diets of overweight individuals can improve chronic disease risk factors. We hypothesized dried plums (DP) would improve nutrient consumption, total antioxidant capacity (TAC), lipid and adipokine profiles, and would decrease adiposity and inflammation. To test this, we studied the effects of 8-weeks of twice-daily snacking of macronutrient-matched 100kcal servings of DP or refined carbohydrate-rich snack (low-fat muffins: LFM) on daily energy and nutrient consumption, and chronic disease risk factors in overweight adults. Body weight/composition, waist circumference, blood pressure, plasma glucose, insulin, c-peptide, lipids, TAC, adipokines and inflammation were measured at baseline and throughout the study. Postprandial glucose and insulin were assessed following assigned test foods at baseline and 8-weeks. Repeated measures ANOVAs were undertaken to examine group and time differences. Post-hoc independent and paired samples t-tests were conducted where necessary. DP increased (P<.05) overall intake of dietary fiber and potassium, and TAC, from baseline to 8-weeks. Baseline postprandial glycemia tended (P=.09) to be lower with DP versus LFM, while both groups had a decreased response after 8-weeks. Postprandial insulinemia was lower (P<.05) for DP at both time-points. No differences in body weight/composition, blood pressure, or fasting glucose, insulin, triglycerides, total cholesterol, HDL-C, inflammation or adipokines were detected. Low-density lipoprotein cholesterol (LDL-C) increased (P<.05) throughout the trial following LFM. Overall, DP lessened postprandial insulinemia, improved nutrient consumption and plasma TAC, and maintained plasma LDL-C compared to a macronutrient-matched refined carbohydrate snack, which could decrease chronic disease risk.

Anti-Inflammatory, Antioxidant, and Hypolipidemic Effects of Mixed Nuts in Atherogenic Diet-Fed Rats.

Nut consumption is associated with reduced risk of cardiovascular disease (CVD). Because most studies have administered single nut varieties, it is unknown whether mixed nuts will also reduce CVD risk. The objective of this study was to compare the effects of mixed nut and pistachio consumption on lipid profiles, glucose, inflammation, oxidative stress, and antioxidant capacity in rats fed an atherogenic diet. Thirty male Sprague-Dawley rats (21 days old) were assigned into three groups (n = 10) based on initial body weight and fed either an isocaloric control diet (no nuts), 8.1% pistachio diet (single nut), or 7.5% mixed nut diet (almonds, brazil nuts, cashews, macadamia nuts, peanuts, pecans, pistachios, and walnuts) for 8 weeks. Both pistachios and mixed nuts significantly decreased triglycerides, total cholesterol, and LDL-cholesterol (p < 0.05) compared with controls. Both nut groups exhibited reductions in C-reactive protein (p = 0.045) and oxidative stress (p = 0.004). The mixed nut group had greater superoxide dismutase (p = 0.004) and catalase (p = 0.044) and lower aspartate aminotransferase (p = 0.048) activities. Gene expression for Fas, Hmgcr, and Cox2 was downregulated for both nut groups compared to controls (p < 0.05). In conclusion, mixed nuts and individual nut varieties have comparable effects on CVD risk factors in rats.

Effects of Watermelon Powder and l-arginine Supplementation on Azoxymethane-Induced Colon Carcinogenesis in Rats.

Diets high in fruits and vegetables may help prevent colorectal cancer (CRC). Watermelon consumption may reduce CRC risk due to its concentration of l-citrulline and its role in endothelial nitric oxide (NO) production. Research suggests that increased NO levels have tumoricidal effects. The purpose of this study was to determine the effects of watermelon powder supplementation on aberrant crypt foci (ACF) formation, precancerous lesions, and expression of genes associated with colon carcinogenesis. Thirty-two male Sprague-Dawley rats were assigned into three groups: control, 0.36% l-arginine, or 0.5% watermelon powder and injected with azoxymethane (15 mg/kg body weight). Both l-arginine and watermelon powder groups exhibited lower total numbers of ACF and high multiplicity ACF (P < 0.01). The watermelon powder group exhibited higher NO levels and lower 8-hydroxyguanosine DNA damage (P < 0.05). Watermelon powder and l-arginine downregulated 8-oxoguanine DNA glycosylase gene expression and upregulated O6-methylguanine DNA methyltransferase gene expression (P < 0.05). Cyclooxgenase-2 gene expression was lower for rats fed with watermelon powder (P < 0.05). These results suggest that watermelon powder or l-arginine supplementation may reduce the risk of colon cancer by suppressing ACF formation through lowering oxidative DNA damage and inflammation, modulating DNA repair enzyme expression, and/or enhancing NO production.

Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms.

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic⁻pituitary⁻adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10⁻80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.

Relationships between physical activity, food choices, gender and BMI in Southern Californian teenagers.

Given the increased prevalence of pediatric obesity and risk of developing chronic disease, there has been great interest in preventing these conditions during childhood by focusing on healthy lifestyle habits, including nutritious eating and physical activity (PA). The purpose of this study was to determine the relationship between PA, body mass index (BMI) and food choices in adolescent males and females. This cross-sectional study, using a survey questionnaire, evaluated 1212 Southern Californian adolescents' self-reported PA, BMI and food frequency. Results revealed that even though males are more active than females, they have higher BMI percentile values (p < 0.05). Females consumed salad, vegetables and fruit more frequently than males (p < 0.05), where males consumed hamburgers, pizza, red meat, processed meat, eggs, fish, fruit juice, soda and whole milk more frequently than females (p < 0.05). Overweight/obese teens consumed red meat, processed meat and cheese more frequently than healthy weight teens (p < 0.05), yet there was no difference in PA between healthy and overweight/obese teens. These results demonstrate that higher levels of PA may not counteract an unhealthy diet. Even though PA provides numerous metabolic and health benefits, this study suggests that healthy food choices may have a protective effect against overweight and obesity. Healthy food choices, along with PA, should be advocated to improve adolescent health by encouraging maintenance of a healthy weight into adulthood.

Effects of moderate alcohol consumption on gene expression related to colonic inflammation and antioxidant enzymes in rats.

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some studies have reported that moderate alcohol consumption may not contribute additional risk for developing colorectal cancer while others suggest that moderate alcohol consumption provides a protective effect that reduces colorectal cancer risk. The purpose of this study was to determine the effects of moderate voluntary alcohol (20% ethanol) intake on alternate days for 3 months in outbred Wistar rats on risk factors associated with colorectal cancer development. Colonic gene expression of cyclooxygenase-2, RelA, 8-oxoguanine DNA glycosylase 1, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase M1, and aldehyde dehydrogenase 2 were determined. Blood alcohol content, liver function enzyme activities, and 8-oxo-deoxyguanosine DNA adducts were also assessed. Alcohol-treated rats were found to have significantly lower 8-oxo-deoxyguanosine levels in blood, a marker of DNA damage. Alanine aminotransferase and lactate dehydrogenase were both significantly lower in the alcohol group. Moderate alcohol significantly decreased cyclooxygenase-2 gene expression, an inflammatory marker associated with colorectal cancer risk. The alcohol group had significantly increased glutathione-S-transferase M1 expression, an antioxidant enzyme that helps detoxify carcinogens, such as acetaldehyde, and significantly increased aldehyde dehydrogenase 2 expression, which allows for greater acetaldehyde clearance. Increased expression of glutathione-S-transferase M1 and aldehyde dehydrogenase 2 likely contributed to reduce mucosal damage that is caused by acetaldehyde accumulation. These results indicate that moderate alcohol may reduce the risk for colorectal cancer development, which was evidenced by reduced inflammation activity and lower DNA damage after alcohol exposure.

Fish Oil Contaminated with Persistent Organic Pollutants Induces Colonic Aberrant Crypt Foci Formation and Reduces Antioxidant Enzyme Gene Expression in Rats.

Background: Epidemiologic, clinical, and experimental studies have suggested that fish oil (FO), a rich source of n-3 (ω-3) polyunsaturated fatty acids, protects against colon cancer. However, this message is confounded by the FDA's warning that the consumption of certain types of fish should be restricted because of contamination with persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and organochlorine pesticides.Objective: We examined FO contaminated with POPs (PCBs, dichlorodiphenyltrichloroethane, and chlordane) compared with unmodified FO on the risk factors of colon cancer development.Methods: Male Sprague-Dawley rats aged 28 d (n = 30) were allocated into 3 groups and fed 15% corn oil (CO), FO, or POP-contaminated FO for 9 wk with a subcutaneous injection of colon carcinogen azoxymethane at weeks 3 and 4. Colonic aberrant crypt foci (ACF) and cell proliferation were enumerated, and the gene expression of inflammation, antioxidant enzymes, and repair enzymes were determined with the use of real-time quantitative polymerase chain reaction analysis.Results: FO-fed rats had a lower number of ACF (mean ± SE: 29 ± 4.0 for FO compared with 53 ± 8.4 for CO and 44 ± 4.6 for POP FO) and higher-multiplicity ACF than the CO and POP FO groups (4.7 ± 0.9 for FO compared with 11 ± 1.5 for CO and 9.6 ± 1.8 for POP FO) (P < 0.05). FO feeding lowered the proliferation index compared with the CO and POP FO feeding groups (18% ± 1.1% for FO compared with 25% ± 1.6% for CO and 23% ± 0.7% for POP FO) (P = 0.009). Superoxide dismutase [2.4 ± 0.6 relative quantification (RQ) for FO compared with 1.2 ± 0.2 RQ for CO and 1.3 ± 0.3 RQ for POP FO] and catalase gene expression (10 ± 2.0 RQ for FO compared with 5.4 ± 1.1 RQ for CO and 6.6 ± 1.5 RQ for POP FO) were higher in the FO group than in the CO and POP FO groups (P < 0.05). There were no differences between CO and POP FO on the variables.Conclusion: These results indicate that POPs in FO reduce the preventive effects of FO on colon carcinogenesis by increasing preneoplastic lesion formation through the downregulation of antioxidant enzyme expression and increasing cell proliferation in rats.

In vivo regulation of colonic cell proliferation, differentiation, apoptosis, and P27Kip1 by dietary fish oil and butyrate in rats.

We have shown that dietary fish oil is protective against experimentally induced colon cancer, and the protective effect is enhanced by coadministration of pectin. However, the underlying mechanisms have not been fully elucidated. We hypothesized that fish oil with butyrate, a pectin fermentation product, protects against colon cancer initiation by decreasing cell proliferation and increasing differentiation and apoptosis through a p27(Kip1)-mediated mechanism. Rats were provided diets of corn or fish oil, with/without butyrate, and terminated 12, 24, or 48 hours after azoxymethane (AOM) injection. Proliferation (Ki-67), differentiation (Dolichos Biflorus Agglutinin), apoptosis (TUNEL), and p27(Kip1) (cell-cycle mediator) were measured in the same cell within crypts in order to examine the coordination of cell cycle as a function of diet. DNA damage (N(7)-methylguanine) was determined by quantitative IHC analysis. Dietary fish oil decreased DNA damage by 19% (P = 0.001) and proliferation by 50% (P = 0.003) and increased differentiation by 56% (P = 0.039) compared with corn oil. When combined with butyrate, fish oil enhanced apoptosis 24 hours after AOM injection compared with a corn oil/butyrate diet (P = 0.039). There was an inverse relationship between crypt height and apoptosis in the fish oil/butyrate group (r = -0.53, P = 0.040). The corn oil/butyrate group showed a positive correlation between p27(Kip1) expression and proliferation (r = 0.61, P = 0.035). These results indicate the in vivo effect of butyrate on apoptosis and proliferation is dependent on dietary lipid source. These results demonstrate the presence of an early coordinated colonocyte response by which fish oil and butyrate protects against colon tumorigenesis.

Moderate Alcohol Consumption and Colorectal Cancer Risk.

BACKGROUND: Heavy alcohol drinking is a risk factor for colorectal cancer (CRC); previous studies have shown a linear dose-dependent association between alcohol intake and CRC. However, some studies suggest that moderate alcohol consumption may have a protective effect, similar to that seen in cardiovascular disease. Other factors may interact with alcohol and contribute additional risk for CRC. We aimed to determine the association between moderate alcohol consumption, limited to 30 g of alcohol per day, by beverage type on CRC risk and to assess the effects of other factors that interact with alcohol to influence CRC risk. METHODS: The PubMed database was used to find articles published between 2008 and 2014 related to alcohol and CRC. Twenty-one relevant articles were evaluated and summarized, including 11 articles reporting on CRC risk associated with moderate intake and 10 articles focusing on genetic interactions associated with alcohol and CRC risk. RESULTS: The association between alcohol and increased risk for CRC was found when intakes exceeded 30 g/d alcohol. Nonsignificant results were consistently reported for intakes <30 g/d. Additional risks for CRC were found to be related to obesity and folate status for regular alcohol consumers. Some significant results suggest that the development of CRC is dependent on the interaction of gene and environment. CONCLUSIONS: The association between the amount of alcohol consumed and the incidence of CRC was not significant at moderate intake levels. Moderate alcohol consumption was associated with a reduced CRC risk in study populations with greater adherence to a Mediterranean diet, where wine contributed substantially to the alcoholic beverage consumed. Other factors such as obesity, folate deficiency, and genetic susceptibility may contribute additional CRC risk for those consuming alcohol. To minimize CRC risk, appropriate recommendations should encourage intakes below 30 g of alcohol each day.

Fish Oil Contaminated with Persistent Organic Pollutants Reduces Antioxidant Capacity and Induces Oxidative Stress without Affecting Its Capacity to Lower Lipid Concentrations and Systemic Inflammation in Rats.

BACKGROUND: Numerous studies have investigated the benefits of fish, fish oil, and ω-3 (n-3) polyunsaturated fatty acids against cardiovascular diseases. However, concern surrounding contamination with persistent organic pollutants (POPs) prompts caution in the recommendation to consume fish and fish oil. OBJECTIVE: The present study compared the effects of fish oil contaminated with polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) on serum lipid profiles, inflammation, and oxidative stress. METHODS: Twenty eight-day-old male Sprague-Dawley rats (n = 30) consumed diets of unmodified fish oil (FO) consisting of 15% fat by weight, persistent organic pollutant-contaminated fish oil (POP FO) (PCBs at 2.40 µg/g; OCs at 3.80 µg/g FO), or corn oil (control; CO) for 9 wk. Lipid profiles and C-reactive protein concentrations were assessed. Hepatic gene expression related to lipid metabolism was determined by real time quantitative polymerase chain reaction analysis. RESULTS: After 9 wk of feeding, accumulation of PCBs and OCs in the fat tissue of the POP FO group compared with the other 2 groups was confirmed (P < 0.01). Both fish oil groups showed greater HDL cholesterol (FO 53 ± 5.3 and POP FO 55 ± 7.7 vs. CO 34 ± 2.3 mg/dL), but lower triglycerides (24 ± 2.8 and 22 ± 3.0 vs. 43 ± 5.6 mg/dL), LDL cholesterol (38 ± 14 and 34 ± 9.2 vs. 67 ± 4.4 mg/dL), and C-reactive protein (113 ± 20 and 120 ± 26 vs. 189 ± 22 µg/dL) compared with the CO group (P < 0.05). Gene expression of fatty acid synthase in both fish oil groups was also less than in the CO group (P < 0.05). However, the POP FO group showed greater lipid peroxidation (5.1 ± 0.7 vs. 2.9 ± 0.9 and 2.6 ± 0.6 µM) and less antioxidant capacity (0.08 ± 0.06 vs. 0.5 ± 0.1 and 0.4 ± 0.1 mM) than the CO and FO groups (P < 0.05). CONCLUSIONS: These findings indicate that, despite exhibiting benefits on serum lipid concentrations and inflammation, contamination with PCBs and OCs showed significant negative effects on oxidative stress and antioxidant capacity in rats. Future studies should investigate the effects of different contaminant doses and the possibility of a dose-dependent response, a lengthened feeding time, and interactions between contaminant mixtures and oils of varying composition to advise on dietary consumption of fish and fish oil.

Watermelon consumption improves inflammation and antioxidant capacity in rats fed an atherogenic diet.

Cardiovascular disease (CVD) is the leading cause of death in the United States. Watermelon, rich in antioxidants and other bioactive components, may be a viable method to improve CVD risk factors through reduced oxidative stress. The purpose of the study was to determine the effects of watermelon powder consumption on lipid profiles, antioxidant capacity, and inflammation in dextran sodium sulfate (DSS)-treated rats fed an atherogenic diet. We hypothesized that watermelon would increase antioxidant capacity and reduce blood lipids and inflammation through modulation of related gene expression. Forty male-weanling (21 days old) Sprague-Dawley rats were divided into 4 groups (10 per group, total N = 40) in a 2 diets (control or 0.33% watermelon) × 2 treatments (with or without DSS) factorial design using an atherogenic diet. Watermelon-fed groups exhibited significantly lower serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol (P< .05). C-reactive protein levels were significantly lower in watermelon-fed rats than the control (P= .001). In addition, oxidative stress as measured by thiobarbituric acid reactive substances was significantly lower in watermelon groups (P= .001). Total antioxidant capacity, superoxide dismutase, and catalase activities were greater in watermelon groups (P< .05). Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were significantly lower in DSS-treated rats when watermelon was consumed (P< .05). Fatty acid synthase, 3-hydroxy-3methyl-glutaryl-CoA reductase, sterol regulatory element-binding protein 1, sterol regulatory element-binding protein 2, and cyclooxygenase-2 gene expression was significantly downregulated in the watermelon group without DSS (P< .05). These findings indicate that watermelon improves risk factors for CVD in rats through better lipid profiles, lower inflammation, and greater antioxidant capacity by altering gene expression for lipid metabolism.

Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.

Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.