Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, Brazil.
Pharm Biol. 2013 Feb;51(2):160-9. doi: 10.3109/13880209.2012.715171. Epub 2012 Nov 2.
Alcohol consumption has been related to a cell proliferation increase in oral epithelium but its mechanism remains unclear.
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.
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.
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.
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.
饮酒与口腔上皮细胞增殖增加有关，但具体机制尚不清楚。
本研究旨在探讨不同时间慢性酒精摄入后，氧化应激参数是否与大鼠舌上皮细胞增殖的诱导有关。
通过 AgNOR（与活跃核仁组织者区域相关的银染蛋白）定量评估舌上皮细胞的增殖。在舌匀浆中定量测定氧化应激参数[脂质过氧化、蛋白羰基、超氧化物歧化酶活性和过氧化氢酶（CAT）活性和免疫含量]和 Nrf2 免疫含量。
酒精摄入 120 天后，舌腹侧上皮的平均 AgNOR 数（mAgNOR）为 2.22±0.30（vs. 对照组动物的 1.87±0.18 和酒精处理 60 天的动物的 1.91±0.23），表明细胞增殖增加（p<0.05，ANOVA 后 Tukey 检验）。有趣的是，60 天的酒精摄入诱导了氧化应激参数的变化，但没有改变细胞增殖。进行了维生素 E 共同处理以评估其可能的保护作用。与 Tween+维生素 E 处理组相比，120 天 Tween+维生素 E+酒精处理诱导 mAgNOR 增加（分别为 2.10±0.30 vs. 1.77±0.11，p<0.05，ANOVA 后 Tukey 检验），表明维生素 E 共同处理没有保护作用。此外，还观察到 CAT 活性与 AgNOR 数量之间存在负相关（R=-0.32；p<0.05，Person 相关），以及 Nrf2 可能参与酒精相关损伤。
我们的发现表明，与酒精相关损伤相关的细胞增殖增加与氧化参数失衡没有直接关系。相反，我们的结果表明，过氧化氢可能与口腔黏膜细胞增殖过程中的细胞信号转导有关。
