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

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.

Meta‐analysis of 16 studies of the association of alcohol with colorectal cancer

“…The mechanisms by which alcohol consumption influences CRC risk are still being explored . The breakdown of alcohol to acetaldehyde, a carcinogen that has been shown to disrupt DNA replication and repair, is widely believed to play a role in CRC risk .…”

“…17 The mechanisms by which alcohol consumption influences CRC risk are still being explored. 13,14,29 The breakdown of alcohol to acetaldehyde, a carcinogen that has been shown to disrupt DNA replication and repair, is widely believed to play a role in CRC risk. 14,30,31 Chronic alcohol consumption has also been shown to disrupt folate metabolism, and folate deficiency is an established risk factor for CRC.…”

“…36 A 2017 study of the effects of moderate alcohol consumption in rats observed that moderate levels of alcohol intake did not elevate biological risk factors for CRC development and may provide beneficial effects through reduced inflammation and lower DNA damage. 29 As we cannot rule out that the inverse association may be explained by residual confounding or chance, a better understanding of the underlying mechanism is necessary to interpret observed protective effects of light/moderate alcohol consumption and inform CRC prevention recommendations.…”

“…6,16,26 We considered the following potential confounders, measured at reference time: age, ethnic group, sex, educational attainment (less than high school graduate, high school graduate or GED, some college or technical school, college graduate or graduate school), body mass index (BMI: kg/m 2 ), physical activity (≥1 hr/week of vigorous/moderate physical activity vs. <1 hr/week), smoking (never vs. ever smoker and pack-years), regular use of aspirin and nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), regular use of postmenopausal hormone therapy (collected only for postmenopausal women), red/processed meat intake, fruit and vegetable intake, folate intake (including dietary and supplements), calcium intake (including dietary and supplements), dietary fiber intake, screening history (history of sigmoidoscopy or colonoscopy), family history of CRC in first-degree relatives, and history of diabetes. BMI was derived using pre-diagnosis (cases) or referent (controls) weight and height and analyzed as both a continuous and categorical variable (underweight or normal [<24.9], overweight, [25][26][27][28][29][30] obese [≥30]). Smoking pack-years were calculated for former or current smokers by multiplying the average number of cigarettes per day by the number of years smoked and dividing by 20 (number of cigarettes in a pack).…”

Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

“…Finally, investigations in rats fed a high-fat high-cholesterol diet showed that a moderate ethanol consumption for 8 weeks alleviated liver fibrosis and reduced the mRNA expression of several profibrotic genes [18]. Notably, the beneficial effects of moderate ethanol exposure in rodents are not restricted to the liver and can also be observed in other organs and tissues such heart, colon, white adipose tissue and blood vessels [19][20][21]. Lower oxidative stress and inflammation as well as improvement of lipid metabolism could be involved in these favorable effects [19][20][21].…”