Influência do pesticida Diclorvós sobre a população de mastócitos e modulação de TNF-α na próstata dorsolateral de ratos.
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Data
2023-02-08
Autores
Santana, Ana Clara Pacheco de
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Universidade Estadual Paulista (Unesp)
Resumo
A próstata é um órgão hormônio-dependente que está sujeito à ação de poluentes ambientais que mimetizam a ação hormonal, conhecidos como desreguladores endócrinos. Dentre estes compostos, está o diclorvós (DDVP), pesticida amplamente utilizado no controle de pragas e potencialmente capaz de promover alterações morfológicas teciduais, levando ao desenvolvimento de processos inflamatórios e lesões precursoras do câncer, por meio da liberação de citocinas, como o fator de necrose tumoral alfa (TNF-α). Os mastócitos são células presentes em inflamações agudas e crônicas, e sua ação anti-inflamatória se dá pela síntese e secreção de mediadores inflamatórios, como TNF-α. Tendo em vista a relação entre TNF-α, mastócitos, inflamação e carcinogênese prostática, o presente estudo teve como objetivo avaliar a presença de mastócitos e a modulação da resposta inflamatória mediada por TNF-α na próstata dorsolateral de ratos tratados com DDVP e submetidos à indução química do câncer por MNU (N-metil-N-nitrosourea). Para isso, foram utilizados 28 ratos machos da linhagem Fischer 344, com idade de 90 dias, os quais foram separados em quatro grupos experimentais: Sham, Sham+DDVP, MNU, MNU+DDVP. Após a eutanásia, o lobo prostático dorsolateral de cada animal foi encaminhado para análise morfológica e histopatológica (coloração por hematoxilina e eosina), contagem de mastócitos (coloração por azul de toluidina) e imuno-histoquímica para TNF-α. Com a análise histopatológica foram descritas lesões do tipo: descolamento epitelial, vacuolização citoplasmática, atrofia epitelial, e pré-malignas como a hiperplasia, displasia e focos inflamatórios. Em relação a presença de mastócitos, também houve um aumento em sua frequência, o mesmo ocorre para a marcação de TNF-α, na qual é visto uma tendência de aumento na expressão nos grupos SD e M. Diante disso, a exposição ao DDVP interfere no processo inflamatório (aumento do infiltrado inflamatório e na expressão do TNF-α) o que pode estar associado ao surgimento das manifestações histopatológicas encontradas na próstata.
The prostate is a hormone-dependent organ that can be disturbed by environmental pollutants, known as endocrine disruptors, that mimetize the hormonal action. Among these compounds is Dichlorvos (DDVP), a pesticide widely used in pest control and potentially capable of promoting tissue morphological changes, consequently developing inflammatory processes and cancer precursor lesions, through the release of cytokines, such as tumor necrosis factor alpha (TNF-α). Mast cells are present in acute and chronic inflammation, with anti-inflammatory action, due the synthesis and secretion of inflammatory mediators, such as TNF-α. In view of the relationship between TNF-α, mast cells, inflammation and prostatic carcinogenesis, this project aimed to evaluate the presence of mast cells and the modulation of the inflammatory response mediated by TNF-α in the dorsolateral prostate of rats treated with DDVP and submitted to chemical induction of cancer by MNU (N-methyl-N-nitrosourea). For this, 28 Fischer 344 male rats, aged 90 days, were used. The rats were separated into four experimental groups: Sham, Sham+DDVP, MNU, MNU+DDVP. After euthanasia, the dorsolateral prostatic lobe of each animal was sent for morphological and histopathological analysis (hematoxylin and eosin staining), mast cell count (toluidine blue staining) and TNF-α immunohistochemistry. With the histopathological analysis, lesions of the type were described: epithelial detachment, cytoplasmic vacuolization, epithelial atrophy, and pre-malignant ones such as hyperplasia, dysplasia, and inflammatory foci. Regarding the presence of mast cells, there was also an increase in their frequency, the same occurs for TNF-α marking, in which a tendency towards increased expression is seen in the SD and M groups. Because of this, exposure to DDVP interferes with the inflammatory process (increase in the inflammatory infiltrate and expression of TNF-α), which may be associated with the appearance of histopathological manifestations found in the prostate.
The prostate is a hormone-dependent organ that can be disturbed by environmental pollutants, known as endocrine disruptors, that mimetize the hormonal action. Among these compounds is Dichlorvos (DDVP), a pesticide widely used in pest control and potentially capable of promoting tissue morphological changes, consequently developing inflammatory processes and cancer precursor lesions, through the release of cytokines, such as tumor necrosis factor alpha (TNF-α). Mast cells are present in acute and chronic inflammation, with anti-inflammatory action, due the synthesis and secretion of inflammatory mediators, such as TNF-α. In view of the relationship between TNF-α, mast cells, inflammation and prostatic carcinogenesis, this project aimed to evaluate the presence of mast cells and the modulation of the inflammatory response mediated by TNF-α in the dorsolateral prostate of rats treated with DDVP and submitted to chemical induction of cancer by MNU (N-methyl-N-nitrosourea). For this, 28 Fischer 344 male rats, aged 90 days, were used. The rats were separated into four experimental groups: Sham, Sham+DDVP, MNU, MNU+DDVP. After euthanasia, the dorsolateral prostatic lobe of each animal was sent for morphological and histopathological analysis (hematoxylin and eosin staining), mast cell count (toluidine blue staining) and TNF-α immunohistochemistry. With the histopathological analysis, lesions of the type were described: epithelial detachment, cytoplasmic vacuolization, epithelial atrophy, and pre-malignant ones such as hyperplasia, dysplasia, and inflammatory foci. Regarding the presence of mast cells, there was also an increase in their frequency, the same occurs for TNF-α marking, in which a tendency towards increased expression is seen in the SD and M groups. Because of this, exposure to DDVP interferes with the inflammatory process (increase in the inflammatory infiltrate and expression of TNF-α), which may be associated with the appearance of histopathological manifestations found in the prostate.
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Palavras-chave
TNF-α, Lesões prostáticas, Diclorvós, Inflamação, Mastócitos, Dichlorvos, Inflammation, Mast cells, TNF-α and prosthetic lesions