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

CONTEXT: Alcohol consumption has been related to a cell proliferation increase in oral epithelium but its mechanism remains unclear. OBJECTIVE: The aim of this study was to investigate whether oxidative stress parameters are implicated in the induction of cell proliferation in rat tongue epithelium after different times of chronic alcohol consumption. MATERIALS AND METHODS: Cell proliferation was assessed in tongue epithelium using AgNOR (argyrophilic proteins related to active nucleolar organizer regions) quantification. Oxidative stress parameters [lipid peroxidation, protein carbonyls, superoxide dismutase activity and catalase (CAT) activity and immunocontent] and Nrf2 immunocontent were quantified in tongue homogenates. RESULTS AND DISCUSSION: Mean AgNOR numbers (mAgNOR) per nucleus was 2.22 ± 0.30 in ventral tongue epithelium after 120 days of alcohol consumption (vs. 1.87 ± 0.18 for control animals and 1.91 ± 0.23 for animals treated with alcohol for 60 days) indicating cell proliferation increase (p < 0.05, ANOVA followed by Tukey post hoc). Interestingly, 60 days of alcohol consumption induced changes in oxidative stress parameters, but no alteration in cell proliferation. Vitamin E co-treatment was conduced in order to evaluate its possible protective effects. The 120 day Tween + vitamin E + alcohol treatment induced an increase in mAgNORs when compared to the Tween + vitamin E treated group (respectively 2.10 ± 0.30 vs. 1.77 ± 0.11, p < 0.05, ANOVA followed by Tukey post hoc), showing that vitamin E co-treatment had no protective effects. In addition, an inverse association was observed between CAT activity and AgNORs quantity (R = -0.32; p < 0.05, Person's correlation) as well as the possible involvement of Nrf2 in alcohol-related damage. CONCLUSIONS: Our findings suggest that the increase in cell proliferation associated with alcohol-related damage has no direct relation with an imbalance in oxidative parameters. In contrast, our results indicate that hydrogen peroxide may be implicated in cellular signaling during proliferation in the oral mucosa.