Genotoxicity and Cytotoxicity Evaluation of UNIVERSIDADE FEDERAL DE GOIÁS INSTITUTE OF BIOLOGICAL SCIENCES Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)- 1Phenylethanone and its Protective Effect Against DNA Damage ALEX LUCAS HANUSCH -MASTER-
2-(4-Nitrophenoxy)-1Phenylethanone NEOLIGNANS Anti-leishmanial, Antifungal Anxiolytic Anti-inflammatory Antitumor Antioxidant activity Reducing ischemic injury Phenylpropanoid Phenylpropanoid 2-(4-Nitrophenoxy)-1Phenylethanone Lignan Neolignan Alex Lucas Hanusch -Master- UFG
GENOTOXICITY and ANTIGENOTOXICITY Many drugs can cause changes in the genetic material, accelerating carcinogenesis and the cell aging process (Kahl et al., 2012). Genotoxic evaluations are conducted during pre-clinical trials (Brambilla & Martelli., 2009). Important factors for lengthening human life span are cancer prevention and tumor control. The development of chemopreventive agents is of great importance to be used in cancer therapies (Rhee & Park, 2001; Lourenço et al., 2010). Alex Lucas Hanusch -Master- UFG
GENOTOXICITY and ANTIGENOTOXICITY The mouse bone marrow micronucleus test is used in genotoxicity and cytotoxicity studies of chemicals. Comet assay or single cell gel electrophoresis is used to genotoxicity evaluation. It is suitable to detect clastogenic compounds, but not aneugenic compounds.
AIM The aim of this study was to evaluate the genotoxic and cytotoxic activities of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) in mice and its protective effect against DNA damage.
Materials and Methods The neolignan analogue 4NF was characterized by nuclear magnetic resonance of 1H and infrared technique, which showed a high degree of purity. Alex Lucas Hanusch -Master- UFG
MOUSE BONE MARROW MICRONUCLEUS TEST Intraperitoneal administration 24 hours and 48 hours. Cyclophosphamide at 50 mg.kg-1 Euthanasia Genotoxicity 2000 PCE Cytotoxicity ratio of PCE and NCE Alex Lucas Hanusch -Master- UFG
COMET ASSAY Electrophoresis (pH > 13) Lysis Electrophoresis (pH > 13) CASP (Comet Assay Software Project) version 1.2.3. It was assessed the DNA damage of 100 nucleoids % DNA in the tail, the tail moment and Olive tail moment Alex Lucas Hanusch -Master- UFG
RESULTS Micronucleus test Alex Lucas Hanusch -Master- UFG 9
RESULTS Micronucleus test Alex Lucas Hanusch -Master- UFG
RESULTS Comet assay Alex Lucas Hanusch - Master- UFG
RESULTS Comet assay Alex Lucas Hanusch -Master- UFG
DISCUSSION No genotoxic effect: micronucleus test and comet assay Studies with neolignans also showed no genotoxic effect induced by these molecules. LI et al (2007) found no genotoxic effects of a plant extract containing 94% of magnolol neolignan and 1.5% of honokiol neolignan. Daurinol and cubebin lignans: Do not present genotoxic effects (Kang et al, 2011; Rezende et al, 2013.). Alex Lucas Hanusch -Master- UFG
DISCUSSION Cytotoxic: reduction ratio of PCE / NCE at a dose of 100mg.kg-1 The cytotoxicity is of great interest in the prevention and treatment of disease and is a promising characteristics for a candidate chemotherapeutic agent. Studies have found lignoids with cytotoxic activity specific for some tumor cell lines, such as neolignan licarin A and the lignans galbacin, sesamin, machilin A and G (Lee et al, 2004;. SAEED et al, 2014). Alex Lucas Hanusch -Master- UFG
DISCUSSION Antigenotoxic and anticytotoxic: Micronucleus and Comet test. OLIVEIRA JÚNIOR et al (2007) They observed a reduction in the number of micronuclei induced by cyclophosphamide in mice treated with grandidisin neolignan. Magnolol neolignans Hinokinin and cubebin lignans They proved to be antimutagenic, antigenotoxic and antioxidants (SAITO et al., 2006; SAITO et al., 2008; MEDOLA et al., 2007; RESENDE et al., 2010; REZENDE et al., 2013; SINIGAGLIA et al., 2006). Alex Lucas Hanusch -Master- UFG
CONCLUSION The 4NF did not exhibit genotoxicity. Reduce cytotoxic and genotoxic effects of cyclophosphamide. The possible use of this compound as a chemopreventive and/or therapeutic agent still requires further investigation using different mutagenicity/genotoxicity tests, long-term tests in animals, and research in molecular biology to carry out comprehensive studies of gene expression. Alex Lucas Hanusch -Master- UFG
Thank you for your attention! Alex Lucas Hanusch -Master- UFG