Efeitos do resveratrol sobre o desenvolvimento e carcinogênese da glândula mamária na prole de ratas da linhagem Wistar expostas a 2,3,7,8-tetraclorodibenzo-p-dioxina (TCDD) na gestação
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Data
2016-07-04
Autores
Silva, Tássia Campos de Lima e [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O resveratrol (RES) destaca-se principalmente por suas propriedades anti-carcinogênica, anti-inflamatória, antioxidante e estrogênica, atuando inclusive como antagonista do receptor aril-hidrocarboneto (AhR). A 2,3,7,8-tetraclorodibenzo-p-dioxina (TCDD) é considerada uma das dioxinas de maior toxicidade, possuindo grande relevância para estudos envolvendo a saúde humana e animal. Sua ação está associada à interação com o receptor aril-hidrocarboneto (AhR), responsável pelos efeitos adversos do TCDD sobre o crescimento e desenvolvimento mamário das mães na gestação/lactação e na prole de fêmeas de mães expostas. Portanto, o presente estudo objetivou identificar a capacidade do RES (gestação/lactação) de alterar os efeitos adversos do TCDD na glândula mamária da prole de fêmeas após exposição gestacional a esta dioxina; avaliar os efeitos isolados ou de associação da exposição ao TCDD (gestação) e ao RES (gestação/lactação) através de parâmetros morfológicos, imunoistoquímicos e moleculares na glândula mamária da prole de fêmeas no dia pós-natal (DPN) 22; avaliar os efeitos maternos do TCDD e/ou do RES sobre a susceptibilidade ao desenvolvimento de câncer de mama induzido pela administração de N-metil-N-nitrosourea (MNU, 50mg/kg no DPN 22 e 51) na vida adulta. Desta forma, fêmeas prenhes da linhagem Wistar foram divididas em quatro grupos experimentais (n=15 cada): Controle, TCDD, TCDD+RES e RES. O TCDD foi administrado em dose única no 15º dia gestacional (DG15) na dose de 1µg/kg e o RES foi administrado do DG10 ao DG21 na dose de 20 mg/Kg, ambos via gavagem. Fêmeas da geração F1 foram eutanasiadas no DPN 22 e DPN 160. No DPN 22, o tratamento materno ao TCDD alterou o desenvolvimento de estrutura mamária, mas sem modificar os niveis de proliferação celular ou expresssão do receptor de estrógeno alfa (RE-α) nas glândulas mamárias, quando comparado ao grupo controle. A análise de expressão gênica indica que alguns genes associados ativação de Ahr (Ahrr) e de apoptose (Bcl-2, Bax e caspase 3) apresentaram-se no grupo TCDD, quando comparado ao grupo controle, sendo os dois primeiros “up” e os ultimos “down” regulados. No DPN 160, maior numero de tumores mamários (multiplicidade) foram observados no grupo TCDD em relação aos demais grupos. De uma forma geral, os resultados indicam que as alterações mamárias induzidas na prole de fêmeas pelo TCDD foram influenciadas pelo tratamento materno com RES.
Resveratrol (RES) stands out primarily for its anti- carcinogenic, anti- inflammatory, antioxidant and estrogenic properties, including acting as an antagonist of aryl hydrocarbon receptor (AhR). The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is considered one of the dioxin with most toxicity, having great relevance to public human and animal health. Its biological action is associated with the interaction with AhR, responsible for the adverse effects of TCDD on mammary growth and development from mothers exposed during pregnancy/lactation and in female offspring. Therefore , this study aimed 1) to identify the capacity of RES (pregnancy/lactation treatment) to modify the adverse effects of TCDD in the mammary gland of female offspring after gestational exposure to this dioxin; 2) to evaluate the isolated effects or the association with TCDD (pregnancy exposure) RES (pregnancy/lactation treatment) through morphological parameters, immunohistochemical and molecular in the mammary gland of female offspring on postnatal day (PND) 22; 3) to identify maternal effects of TCDD and/or the RES on the susceptibility to the development of mammary cancer induced by administration of N- methyl-N- nitrosourea (MNU, 50mg/kg PND 22 and 51) in adulthood. Thus, pregnant female Wistar were divided into four groups (n=15 each): Control, TCDD, TCDD + RES and RES. TCDD was orally administered as a single dose on gestational day 15 (GD15) at 1µg/kg and RES was orally administered during GD10 to GD21 daily at dose of 20 mg/kg. Female F1 generation was euthanized at PND 22 to PND 160. At PND 22, Maternal TCDD exposure altered the development of mammary structure, but without modifying the cell proliferation or estrogen receptor alpha (ER -α) levels in the mammary glands when compared to the control group. Gene expression analysis indicates that some genes associated activation Ahr (Ahrr) and apoptosis (Bcl -2, Bax and caspase 3) were altered in the TCDD group compared to the control group, being the first two "up" and the last "down" regulated. At PND 160, a higher number of mammary tumors (multiplicity) were observed in TCDD group compared to other groups. Overall, the results indicate the mammary changes induced in the female offspring due to maternal TCDD exposure were influenced by maternal RES treatment.
Resveratrol (RES) stands out primarily for its anti- carcinogenic, anti- inflammatory, antioxidant and estrogenic properties, including acting as an antagonist of aryl hydrocarbon receptor (AhR). The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is considered one of the dioxin with most toxicity, having great relevance to public human and animal health. Its biological action is associated with the interaction with AhR, responsible for the adverse effects of TCDD on mammary growth and development from mothers exposed during pregnancy/lactation and in female offspring. Therefore , this study aimed 1) to identify the capacity of RES (pregnancy/lactation treatment) to modify the adverse effects of TCDD in the mammary gland of female offspring after gestational exposure to this dioxin; 2) to evaluate the isolated effects or the association with TCDD (pregnancy exposure) RES (pregnancy/lactation treatment) through morphological parameters, immunohistochemical and molecular in the mammary gland of female offspring on postnatal day (PND) 22; 3) to identify maternal effects of TCDD and/or the RES on the susceptibility to the development of mammary cancer induced by administration of N- methyl-N- nitrosourea (MNU, 50mg/kg PND 22 and 51) in adulthood. Thus, pregnant female Wistar were divided into four groups (n=15 each): Control, TCDD, TCDD + RES and RES. TCDD was orally administered as a single dose on gestational day 15 (GD15) at 1µg/kg and RES was orally administered during GD10 to GD21 daily at dose of 20 mg/kg. Female F1 generation was euthanized at PND 22 to PND 160. At PND 22, Maternal TCDD exposure altered the development of mammary structure, but without modifying the cell proliferation or estrogen receptor alpha (ER -α) levels in the mammary glands when compared to the control group. Gene expression analysis indicates that some genes associated activation Ahr (Ahrr) and apoptosis (Bcl -2, Bax and caspase 3) were altered in the TCDD group compared to the control group, being the first two "up" and the last "down" regulated. At PND 160, a higher number of mammary tumors (multiplicity) were observed in TCDD group compared to other groups. Overall, the results indicate the mammary changes induced in the female offspring due to maternal TCDD exposure were influenced by maternal RES treatment.
Descrição
Palavras-chave
Exposição gestacional/lactacional, 2,3,7,8-tetraclorodibenzo-p-dioxina (TCDD), Resveratrol, Desenvolvimento mamário, Carcinogênese mamária, Pregnancy/lactation exposure, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Resveratrol, Mammary gland development and carcinogenesis