Inhibition of Alcohol-Associated Colonic Hyperregeneration by ??-Tocopherol in the Rat

Abstract

Alcohol-associated hyperproliferation could be prevented, at least in part, by supplementation with alpha-tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol-associated colorectal hyperproliferation.

DNA/RNA Markers for Colorectal Cancer Risk in Preserved Stool Specimens: A Pilot Study

“…The association with alcohol intake is intriguing, as alcohol intake has been convincingly associated with an increased risk of colorectal cancer, especially for men 17 . In support of this association, increased cell regeneration and proliferation has been observed in experimental animals treated with ethanol as well as in chronic alcoholic patients 43-45 . These effects of alcohol have been hypothesized to be medicated through prostaglandin production (via COX), lipid peroxidation, generation of reactive oxygen species, and proinflammatory cytokine induction 17,46,47 .…”

Exploring the mechanisms of alcohol-related damage in oral mucosa – is oxidative stress associated with the increase in cell proliferation in rat tongue epithelium?

“…In this study, Tween 80 was chosen because: (i) it allows the preparation of a water-soluble mixture, which was suitable in order to improve gastrointestinal absorption and (ii) it was used in other studies (Krishnamurthy & Bieri, 1963;Ilavazhagan et al, 2001) without any adverse effects. Unfortunately, since Tween reduced Nrf2, suggesting a pro-oxidant effect, the antioxidant (Krishnamurthy & Bieri, 1963;Ilavazhagan et al, 2001;Kalender et al, 2004) and/or antiproliferative (Vincon et al, 2003) effects of vitamin E could not be properly evaluated in this study. Furthermore, our findings indicate that signaling for cell proliferation occurs by means of hydrogen peroxide in oral mucosa, which is in accordance with previous studies in other tissues (Burdon, 1995;Li & Spector, 1997).…”

“…A lower grade of keratinization and a longer contact with the ingested alcohol may also contribute to this effect. Vincon et al (2003) reversed the increase in alcoholrelated proliferation in the colon mucosa of rats by means of vitamin E supplementation. In our study, the protective effects of vitamin E were found only in terms of attenuation of alcohol-related decrease in Nrf2 immunocontent.…”

“…In addition, Nrf2, a redox-sensitive transcription factor involved in antioxidant defenses which is usually associated to the response to xenobiotics (Motohashi & Yamamoto, 2004), could be involved in the pathogenesis of alcohol-induced cell and tissue damage. Vincon et al (2003) demonstrated that vitamin E supplementation attenuates the increased epithelial proliferation in rat colon mucosa due to alcohol intake. This could be associated with antioxidant properties of vitamin E. However, the mechanisms relating chronic alcohol consumption and cell proliferation increase in oral epithelial cells remains unknown.…”

Phosphatidylethanol Accumulation Promotes Intestinal Hyperplasia by Inducing ZONAB-Mediated Cell Density Increase in Response to Chronic Ethanol Exposure

“…Yet, some of these effects have been described using the Caco-2 colorectal carcinoma cell line (8), which do not express any ADH (13), suggesting that one or several other metabolic pathways could play a role in the tumor-promoting activity of ethanol. As an example, free radicals generated from ethanol metabolism are thought to play a role in the pathogenesis of alcohol-associated colorectal hyperproliferation (14). Furthermore, ethanol could also undergo chemical coupling to membrane phospholipids via the action of phospholipase D (PLD; refs.…”