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

ABSTRACT: 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.

SUBMITTER: Wells N

PROVIDER: S-EPMC7743962 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Wells Nicole N Quigley Jacqueline J Pascua Jeremy J Pinkowski Natalie N Almaiman Lama L Brasser Susan M SM Hong Mee Young MY

PloS one 20201216 12

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-mode ...[more]

PMID: 33326448

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Project description:Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor (CIE) and ethanol drinking (ED) procedure. During the last week of CIE, a subset of male and female TK rats was fed valcyte to ablate dividing progenitor cells and continued the diet until the end of this study. Following week six, all CIE rats experienced two weeks of forced abstinence from CIE-ED, after which they experienced relapse to drinking, extinction, and reinstatement of ethanol seeking sessions. CIE increased ED in female and male rats, with females having higher ethanol consumption during CIE and relapse sessions compared with males. In both sexes, valcyte reduced the levels of Ki-67-labeled progenitor cells in the subgranular zone of the dentate gyrus and did not alter the levels in the medial prefrontal cortex (mPFC). Valcyte increased ED during relapse, increased lever responses during extinction and, interestingly, enhanced latency to extinguish ethanol-seeking behaviors in males. Valcyte reduced the reinstatement of ethanol-seeking behaviors triggered by ethanol cues in females and males. Reduced seeking by valcyte was associated with the normalization of cytokines and chemokines in plasma isolated from trunk blood, indicating a role for progenitor cells in peripheral inflammatory responses. Reduced seeking by valcyte was associated with increases in tight junction protein claudin-5 and oligodendrogenesis in the dentate gyrus and reduction in microglial activity in the dentate gyrus and mPFC in females and males, demonstrating a role for progenitor cells in the dentate gyrus in dependence-induced endothelial and microglial dysfunction. These data suggest that progenitor cells born during withdrawal and abstinence from CIE in the dentate gyrus are aberrant and could play a role in strengthening ethanol memories triggered by ethanol cues via central and peripheral immune responses.

Project description:BACKGROUND:Preterm delivery has been shown to be associated with increased risk of cardiovascular disease (CVD), but it is unknown whether this risk remains after adjustment for prepregnancy lifestyle and CVD risk factors. METHODS:We examined the association between history of having delivered an infant preterm (<37 weeks) and CVD in 70?182 parous women in the Nurses' Health Study II. Multivariable Cox proportional-hazards models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for CVD events (myocardial infarction and stroke, n=949); we also adjusted for intermediates to determine the proportion of the association between preterm and CVD accounted for by postpartum development of CVD risk factors. RESULTS:After adjusting for age, race, parental education, and prepregnancy lifestyle and CVD risk factors, preterm delivery in the first pregnancy was associated with an increased risk of CVD (HR, 1.42; 95% CI, 1.16-1.72) in comparison with women with a term delivery (?37 weeks) in the first pregnancy. When preterm delivery was split into moderate preterm (?32 to <37 weeks) and very preterm (<32 weeks), the HRs were 1.22 (95% CI, 0.96-1.54) and 2.01 (95% CI, 1.47-2.75), respectively. The increased rate of CVD in the very preterm group persisted even among women whose first pregnancy was not complicated by hypertensive disorders of pregnancy (HR, 2.01; 95% CI, 1.38-2.93). In comparison with women with at least 2 pregnancies, all of which were delivered at term, women with a preterm first birth and at least 1 later preterm birth had a HR of CVD of 1.65 (95% CI, 1.20-2.28). The association between moderate preterm first birth and CVD was accounted for in part by the development of postpartum chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index (proportion accounted for, 14.5%; 95% CI, 4.0-41.1), as was the very-preterm-CVD relationship (13.1%; 95% CI, 9.0-18.7). CONCLUSIONS:Preterm delivery is independently predictive of CVD and may be useful for CVD prevention efforts. Because only a modest proportion of the preterm-CVD association was accounted for by development of conventional CVD risk factors, further research may identify additional pathways.

Dataset Information

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

Publications

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

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