title: Rate of oxidant stress regulates balance between rat gastric mucosa proliferation and apoptosis.
abstract: We have characterized an experimental model of ethanol-induced chronic gastritis in which a compensatory mucosal cell proliferation is apparently regulated by lipoperoxidative events. Therefore, the present study is an attempt to further assess the participation of oxidant stress during gastric mucosa proliferation, by administering alpha-tocopherol (vitamin E) to rats with gastritis. A morphometric analysis was done, and parameters indicative of oxidant stress, cellular proliferation (including cyclin D1 levels), apoptotic events, and activities of endogenous antioxidant systems were measured in gastric mucosa from our experimental groups. After ethanol withdrawal, restitution of surface epithelium coincided with increased lipid peroxidation and cell proliferation and further active apoptosis. High alpha-tocopherol dosing (100 IU/kg bw) showed a clear antioxidant effect, abolished cell proliferation, and promoted an early and progressive apoptosis, despite vitamin E also enhancing levels of endogenous antioxidants. Indicators of cell proliferation inversely correlated with apoptotic events, and this relationship was blunted by administering vitamin E, probably by affecting translocation of active cyclin D1 into the nucleus. In conclusion, alpha-tocopherol administration inhibited cell proliferation, leading to a predominance of apoptotic events in ethanol-induced gastric damage. Therefore, the timing and magnitude of lipoperoxidative events seemed to synchronize in vivo cell proliferative and apoptotic events, probably by changing the cell redox state.
authors.affiliation: Departamento de Biología Celular y Departamento de Bioquímica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-243, México 04510, DF, Mexico.
authors.forename: Marisela
authors.initials: M
authors.lastname: Olguín-Martínez
authors.forename: Edgar
authors.initials: E
authors.lastname: Mendieta-Condado
authors.forename: Martha
authors.initials: M
authors.lastname: Contreras-Zentella
authors.forename: José E
authors.initials: JE
authors.lastname: Escamilla
authors.forename: Alberto
authors.initials: A
authors.lastname: Aranda-Fraustro
authors.forename: Mohammed
authors.initials: M
authors.lastname: El-Hafidi
authors.forename: Rolando
authors.initials: R
authors.lastname: Hernández-Muñoz
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005756:Gastritis / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D019938:Cyclin D1; D014810:Vitamin E; D004247:DNA; D024502:alpha-Tocopherol