title: Exploring the mechanisms of alcohol-related damage in oral mucosa - is oxidative stress associated with the increase in cell proliferation in rat tongue epithelium?
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, Brazil. vcarrard@yahoo.com.br
authors.forename: Vinicius C
authors.initials: VC
authors.lastname: Carrard
authors.forename: Aline S
authors.initials: AS
authors.lastname: Pires
authors.forename: Marina
authors.initials: M
authors.lastname: Mendez
authors.forename: Matheus A B
authors.initials: MA
authors.lastname: Pasquali
authors.forename: Cristiano M
authors.initials: CM
authors.lastname: Badauy
authors.forename: Isabel S
authors.initials: IS
authors.lastname: Lauxen
authors.forename: José Cláudio F
authors.initials: JC
authors.lastname: Moreira
authors.forename: Manoel
authors.initials: M
authors.lastname: Sant'ana Filho
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014059:Tongue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D034961:Antigens, Nuclear; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C051963:nucleolar organizer region associated proteins; D014810:Vitamin E; D000431:Ethanol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase