title: Vitamin E supplementation in chemical colorectal carcinogenesis: a two-edged knife.
abstract: This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF) incidence, oxidative stress parameters (serum and hepatic VE concentration, and homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for two weeks (40 mg/kg), except for the Control group. Animals were separated into groups that received different amounts of VE in the diet: 0 IU (0×), 75 IU (recommended daily intake, RDI), 225 IU (3× RDI), or 1500 IU (20× RDI), during (dDMH) or after (aDMH) administration of carcinogen. The 0×dDMH and 3×dDMH groups showed decreased serum VE levels. Hepatic VE concentration was higher in 3×aDMH as compared with the other groups. All the groups, except the Control and the 0×aDMH groups, had reduced GSH levels. The 0×dDMH, 0×aDMH, and 20×aDMH groups exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA expression. The 0×aDMH group presented higher ACF rate, followed by 20×aDMH. Moreover, the 3×aDMH group displayed reduced ACF incidence and COX2 expression. Multivariate analysis revealed that GSH modulated homocysteine levels and COX2. These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has beneficial effects on chemical colorectal carcinogenesis.
authors.affiliation: Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto14049-900, Brazil. celiacohen@gmail.com.
authors.forename: Celia
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil. jfcardoso@usp.br.
authors.forename: João Felipe Rito
authors.initials: JF
authors.lastname: Cardoso
authors.affiliation: Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil. sbgarcia@fmrp.usp.br.
authors.forename: Sergio Britto
authors.initials: SB
authors.lastname: Garcia
authors.affiliation: Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto14049-900, Brazil. hvannucc@fmrp.usp.br.
authors.forename: Helio
authors.initials: H
authors.lastname: Vannucchi
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000633:toxicity; D058739:Aberrant Crypt Foci / Q000188:drug therapy; D000818:Animals; D015415:Biomarkers / Q000097:blood; D063646:Carcinogenesis / Q000187:drug effects*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064167:Recommended Dietary Allowances; D014810:Vitamin E / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D006710:Homocysteine; D014810:Vitamin E; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005978:Glutathione; D019813:1,2-Dimethylhydrazine