PESTICIDE DICHLORVOS PROMOTES CHANGES IN IMMUNOLOCALIZATION OF INFLAMMATORY MEDIATORS IN VENTRAL PROSTATE OF RATS AFTER CHEMICAL INDUCTION BY MNU

Abstract

Organophosphorus pesticides, such as dichlorvos (DDVP), are widely used in agricultural, commercial, industrial and domestic areas, even though there are many studies that prove their action as endocrine disruptors. They are able to interfere with homeostasis maintained by hormones, disrupting the hypothalamic‐pituitary‐testicular axis and inducing inflammation.Inflammation stimulates carcinogenesis, causing damage to cells and the genome, promoting cell replacement and creating a tissue microenvironment rich in cytokines and growth factors that may increase cell replication, angiogenesis, and repair tissue. The inflammatory process predisposes individuals to various types of cancer, as it induces the production of cytokines such as Tumor necrosis factor alpha (TNFα) which is involved in the development of prostate cancer. Inflammation can be triggered by Toll‐Like receptors (TLRs) which may result in the activation of, for example, Nuclear factor kappa B (NFκB), which plays an important role in cancer responses, inflammation, stress and cell differentiation.Thus, the objective of this work was to evaluate the immunolocalization of inflammatory mediators such as TNFα, TLR4 and NFκB in the ventral prostate of rats after exposure to DDVP, associated or not with chemical induction by N‐methyl‐N‐nitrosourea (MNU).A total of 40 rats of the Fischer 344 strain were used, at the age of 90 days. Rats were randomly assigned to four experimental groups: Sham (G1), Sham + DDVP (G2), MNU (G3), MNU + DDVP (G4). For chemical induction, G3 and G4 were inoculated with MNU at 15 mg / kg, followed by daily subcutaneous injections of 2.5 mg / kg of testosterone cypionate for 20 days. Animals of the G2 and G4 groups, from 120 to 240 days old, received the basal diet supplemented with 10 mg / kg of DDVP. Immunohistochemical analysis of the ventral prostate were performed.TNFα was detected in the whole cytoplasm of luminal epithelial cells in the ventral prostate of all experimental groups, with intense immunoreactivity in the apical region and moderate immunoreactivity in the region of the Golgi apparatus of these cells. The G1 group showed TNFα nuclear localization (fig. 1).The presence of TLR4 in luminal epithelial cells was detected. In groups G1, G2 and G3 there was immunolabeling in the whole cytoplasm of the cells, being the most intense expression in the Golgi apparatus region. In the G4 group, there was immunolabeling in the whole cytoplasm as well, but with moderate intensity in the Golgi apparatus and intense in the apical membrane of the cells (fig. 2).In all experimental groups, NFkB was immunolocalized in the whole cytoplasm of luminal epithelial cells in the ventral prostate. In addition, the G1 and G2 groups showed intense immunoreactivity in the apical region and only the G3 and G4 groups showed immunoreactivity in the perinuclear region and in the nuclear envelope (fig. 3).Thus, we can conclude that exposure to DDVP may alter the immunolocalization pattern of inflammatory mediators, such as NFκB, TNFα and TLR4. And, when associated DDVP with chemical induction by MNU, these changes are accentuated.Support or Funding InformationFAPESP 2017/08505‐5This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.