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1.
Nutr Cancer ; 70(6): 938-945, 2018.
Article in English | MEDLINE | ID: mdl-30207495

ABSTRACT

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.


Subject(s)
Arginine/administration & dosage , Citrullus , Colonic Neoplasms/prevention & control , 8-Hydroxy-2'-Deoxyguanosine , Aberrant Crypt Foci/prevention & control , Animals , Azoxymethane , Cyclooxygenase 2/genetics , DNA Damage , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Dietary Supplements , Male , Nitric Oxide/biosynthesis , Powders , Precancerous Conditions/prevention & control , Rats , Rats, Sprague-Dawley
2.
Alcohol ; 61: 25-31, 2017 06.
Article in English | MEDLINE | ID: mdl-28599714

ABSTRACT

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.


Subject(s)
Alcohol Drinking , Antioxidants/analysis , Colitis/epidemiology , Ethanol/administration & dosage , Gene Expression/drug effects , 8-Hydroxy-2'-Deoxyguanosine , Aldehyde Dehydrogenase, Mitochondrial/genetics , Animals , Colitis/prevention & control , Colorectal Neoplasms/prevention & control , Cyclooxygenase 2/genetics , DNA Damage/drug effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Ethanol/blood , Glutathione Transferase/genetics , Inflammation/genetics , Liver/enzymology , Male , Rats , Rats, Wistar , Risk Factors
3.
Food Funct ; 7(10): 4175-4187, 2016 Oct 12.
Article in English | MEDLINE | ID: mdl-27506987

ABSTRACT

Activation of angiotensin II (Ang II) signaling during aging increases reactive oxygen species (ROS) leading to vascular senescence, a process linked to the onset and progression of cardiovascular diseases (CVD). Consumption of fruits and vegetables, particularly berries, is associated with decreased incidence of CVD, which has mainly been attributed to the polyphenol content of these foods. Thus, the objective of this study was to investigate the role of blackberry (BL), raspberry (RB), and black raspberry (BRB) polyphenol extracts in attenuating Ang II-induced senescence in vascular smooth muscle cells (VSMCs) and to determine the molecular mechanisms involved. BL, RB and BRB polyphenol extracts (200 µg ml-1) attenuated Ang II-induced senescence, denoted by decreased number of cells positive for senescence associated ß-galactosidase (SA-ß-gal) and down-regulation of p21 and p53 expression, which were associated with decreased ROS levels and Ang II signaling. BL polyphenol extract increased superoxide dismutase (SOD) 1 expression, attenuated the up-regulation of Nox1 expression and the phosphorylation of Akt, p38MAPK and ERK1/2 induced by Ang II, and reduced senescence in response to Nox1 overexpression. In contrast, RB and BRB polyphenol extracts up-regulated the expression of SOD1, SOD2, and glutathione peroxidase 1 (GPx1), but exerted no effect on Nox1 expression nor on senescence induced by Nox1 overexpression. BRB reduced signaling similar to BL, while RB was unable to reduce Akt phosphorylation. Furthermore, we demonstrated that inhibition of Akt, p38MAPK and ERK1/2 as well as down-regulation of Nox1 by siRNA prevented senescence induced by Ang II. Our findings indicate that Ang II-induced senescence is attenuated by BL polyphenols through a Nox1-dependent mechanism and by RB and BRB polyphenols in a Nox1-independent manner, likely by increasing the cellular antioxidant capacity.


Subject(s)
Aging/drug effects , Angiotensin II/pharmacology , Muscle, Smooth, Vascular/cytology , Plant Extracts/pharmacology , Polyphenols/chemistry , Polyphenols/pharmacology , Rubus/chemistry , Animals , Aorta , Cells, Cultured , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley , Signal Transduction
4.
Per Med ; 13(3): 265-277, 2016 May.
Article in English | MEDLINE | ID: mdl-29767609

ABSTRACT

BACKGROUND: Interest is growing in the use of genetic risk testing for lifestyle-related chronic diseases, including obesity, to promote health behavior change. OBJECTIVE: A systematic review of the literature was conducted to determine the effects that genetic risk feedback for obesity may have on psychological and behavioral factors influencing weight. METHODS: The MEDLINE/PubMed online database was searched using predefined search terms. RESULTS: The studies revealed that risk feedback may increase motivation to improve health behaviors, especially among individuals at higher genetic risk. Overweight and obese individuals seemed to experience additional psychological benefits when provided an external explanation for their weight status. CONCLUSION: While the psychological benefits are promising, the clinical utility of genetic risk testing for obesity remains uncertain.

5.
Alcohol Clin Exp Res ; 39(8): 1280-91, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26110674

ABSTRACT

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.


Subject(s)
Alcohol Drinking/epidemiology , Alcohol Drinking/trends , Alcoholic Beverages , Colorectal Neoplasms/epidemiology , Alcohol Drinking/adverse effects , Alcoholic Beverages/adverse effects , Case-Control Studies , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Diet, Mediterranean , Humans , Risk Factors , Wine/adverse effects
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