title: Protective effect of metformin in an aberrant crypt foci model induced by 1,2-dimethylhydrazine: Modulation of oxidative stress and inflammatory process.
abstract: Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.
authors: Laboratory of Molecular Pathology, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Heloíza Paranzini
authors: HP
authors: Bordini
authors: Laboratory of Molecular Pathology, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Jean Lucas
authors: JL
authors: Kremer
authors: Laboratory of Molecular Pathology, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Tatiane Renata
authors: TR
authors: Fagundes
authors: Laboratory of Pathophysiology of Free Radicals, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Gabriella Pasqual
authors: GP
authors: Melo
authors: Laboratory of Parasitology, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Ivete
authors: I
authors: Conchon-Costa
authors: Laboratory of Parasitology, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Suelen Santos
authors: SS
authors: da Silva
authors: Laboratory of Pathophysiology of Free Radicals, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Alessandra Lourenço
authors: AL
authors: Cecchini
authors: Laboratory of Inflammatory Mediators, Center of Healthy Sciences, State University of West Parana, Francisco Beltrão, Brazil.
authors: Carolina
authors: C
authors: Panis
authors: Laboratory of Molecular Pathology, Department of Sciences of Pathology, State University of Londrina, Londrina, Brazil.
authors: Rodrigo Cabral
authors: RC
authors: Luiz
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D008687:Metformin; D055372:AMP-Activated Protein Kinases; D019813:1,2-Dimethylhydrazine
keywords: 1,2-dimethylhydrazine; aberrant crypt foci; colorectal cancer; metformin; prevention