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.

Keywords: Alcohol; Colorectal cancer; DNA damage; Inflammation; Moderate.

Fig. 1. Alcohol intake levels

Ethanol intake (g/kg) (A) and 20% ethanol and water intake (mL/kg) (B) in male Wistar rats across all 15 session blocks of ethanol exposure (45 sessions total) in an intermittent-access 20% ethanol drinking paradigm. Individual session data were averaged in 3-session blocks prior to analysis. Values are means ± SEs, n = 12.

Fig. 2. Colonic biomarker gene expression

Gene expression measured from the colon mucosa in male Wistar rats that consumed water (control) or moderate voluntary alcohol (20% ethanol) on alternate days for 13 weeks. Values are means ± SEs, n = 12 per group. *p < 0.05 compared with the controls. ALDH2, aldehyde dehydrogenase 2; COX-2, cyclooxygenase-2; GSTM1, glutathione-S-transferase M1.

Fig. 3. DNA damage measured in serum

DNA damage expressed as 8-oxo-dG was measured in male Wistar rats that consumed water (control) or moderate voluntary alcohol (20% ethanol) on alternate days for 13 weeks. Values are means ± SEs, n = 12 per group. *p < 0.05 compared with the controls. 8-oxo-dG, 8-oxo-deoxyguanosine.