title: Protective effects of the exopolysaccharide Lasiodiplodan against DNA damage and inflammation induced by doxorubicin in rats: Cytogenetic and gene expression assays.
abstract: The lasiodiplodan (LS) is a β-(1→6)-d-glucan produced by the fungus Lasiodiplodia theobromae and some of the biological activities of LS were reported as hypoglycemic, anticoagulant, anti-proliferative and anticancer action; however, its effects on DNA instability and modulation of gene expression are still unclear. Aims of study were investigate the genotoxic effects of lasiodiplodan, and its protective activity against DNA damage induced by doxorubicin (DXR) and its impact on the expression of genes associated with DNA damage and inflammatory response pathways. Therefore, Wistar rats were treated (15 days) orally with LS (5.0; 10 and 20mg/kg bw) alone and in combination with DXR (15mg/kg bw; administrated intraperitoneally on 14th day) as well as their respective controls: distilled water and DXR. Monitoring of DNA damage was assessed by comet and micronucleus (MN) assays and gene expression was evaluated by PCR-Arrays. Treatments with LS alone did not induce disturbances on DNA; when LS was given in combination with DXR, comet and MN formations were reduced to those found in the respective controls. Moreover, LS was able to reduce the disturbances on gene expressions induced by DXR treatment, since the animals that receive LS associated with DXR showed no alteration in the expression of genes related to DNA damage response. Also, DXR induced several up- and down-regulation of several genes associated to inflammatory process, while the animals that received LS+DXR had their gene expression patterns similar to those found in the control group. In conclusion, our results showed that LS did not induce disturbances on DNA stability and significantly reduce the DNA damage and inflammation caused by DXR exposure. In addition, we give further information concerning the molecular mechanisms associated to LS protective effects which seems to be a promising nutraceutical with chemopreventive potential.
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: M B
authors.initials: MB
authors.lastname: Mello
authors.affiliation: Department of Genetics; School of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: C S
authors.initials: CS
authors.lastname: Machado
authors.affiliation: Department of Genetics; School of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: D L
authors.initials: DL
authors.lastname: Ribeiro
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: A F
authors.initials: AF
authors.lastname: Aissa
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: R V
authors.initials: RV
authors.lastname: Burim
authors.affiliation: Department of Chemistry, Federal University of Technology of Paraná, Via do Conhecimento, km 01, CEP 85503-390, Pato Branco, Paraná, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Alves da Cunha
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil; Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Rua Silva Jardim, 136, CEP 11015-020, Santos, São Paulo, Brazil. Electronic address: gustavo.barcelos@unifesp.br.
authors.forename: G R M
authors.initials: GR
authors.lastname: Barcelos
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: L M G
authors.initials: LM
authors.lastname: Antunes
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n°, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: M L P
authors.initials: ML
authors.lastname: Bianchi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D020732:Cytogenetic Analysis / Q000379:methods; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D062610:Fungal Polysaccharides / Q000494:pharmacology*; D015870:Gene Expression; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015025:Zearalenone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D062610:Fungal Polysaccharides; D018836:Inflammation Mediators; D020011:Protective Agents; C417552:lasiodiplodin; D015025:Zearalenone; D004317:Doxorubicin
keywords: Antigenotoxic effects; DNA-damage; Gene expression; Inflammation; Lasiodiplodan; Nutraceuticals