Long exposure to a mixture of endocrine disruptors prediposes the ventral prostate of rats to preneoplastic lesions.

Endocrine disruptors (ED) are compounds dispersed in the environment that modify hormone biosynthesis, affecting hormone-dependent organs such as the prostate. Studies have only focused on evaluating the effects of ED alone or in small groups and short intervals and have not adequately portrayed human exposure. Therefore, we characterized the prostate histoarchitecture of rats exposed to an ED mixture (ED Mix) mimicking human exposure. Pregnant females of the Sprague-Dawley strain were randomly distributed into two experimental groups: Control group (vehicle: corn oil, by gavage) and ED Mix group: received 32.11 mg/kg/day of the ED mixture diluted in corn oil (2 ml/kg), by gavage, from gestational day 7 (DG7) to post-natal day 21 (DPN21). After weaning at DPN22, the male pups continued to receive the complete DE mixture until they were 220 days old when they were euthanized. The ED Mix decreased the epithelial compartment, increased the fractal dimension, and decreased glandular dilation. In addition, low-grade prostatic intraepithelial neoplasia was observed in addition to regions of epithelial atrophy in the group exposed to the ED Mix. Exposure to the mixture decreased both types I and III collagen area in the stroma. We concluded that the ED Mix was able to cause alterations in the prostatic histoarchitecture and induce the appearance of preneoplastic lesions.

Prostate histological investigation in rats exposed to bisphenol a and phytochemicals during the perinatal period and subjected to hormonal stimulus in adulthood.

Bisphenol A (BPA) is an environmentally dispersed chemical associated with tumor development. Phytochemicals such as indole-3-carbinol (I3C) and genistein (GEN) have chemoprotective effects on tumor cells. Thus, this study aimed to evaluate the prostatic morphological aspects of rats exposed to BPA, GEN, and I3C during the perinatal period and submitted to hormonal stimulus in adulthood. Blood was collected to obtain hormone concentrations. Slides stained with hematoxylin & eosin, and picrosirius were subjected to fractal, stereological, morphometric, and collagen quantification analysis. I3C decreased the plasma dihydrotestosterone levels, and both phytochemicals increased the plasma estrogen levels. Unlike phytochemicals, BPA did not alter any of the parameters evaluated. GEN reduced the epithelial height, while I3C increased the fractal dimension and stromal collagen. Although BPA did not alter the prostate morphology, the phytochemicals provided beneficial effects for the prostate histological organization in adult animals subjected to hormonal stimulus.

Are Serum Ferritin Levels a Reliable Cancer Biomarker? A Systematic Review and Meta-Analysis.

Although serum ferritin (SF) has been shown in several studies to be a potential cancer biomarker, the results are inconsistent. Herein, a systematic review was performed to investigate the clinical SF levels in different types of tumors in order to verify the role of SF levels as a biomarker for cancer diagnosis. The search was performed using the PubMed/Medline, Cochrane Library, and Scopus databases. Observational studies comparing SF levels between healthy adults and patients with cancer were included. The meta-analysis was carried out according to the inverse variance and random effects model. The standardized mean differences (SMDs) were assessed at 95% confidence intervals (CIs). We found that SF was higher in patients with cancer (SMD 3.07; CI 1.96,4.17), especially for head and neck cancer (SMD 3.88; CI 0.42,7.34), lung cancer (SMD 1.72; CI 0.67,2.78), pancreatic cancer (SMD 6.79; CI 5.66,7.91), and renal cell carcinoma (SMD 1.77; CI 0.48,3.05). Moreover, in the advanced stages (Stages III and IV), ferritin levels were higher than in healthy adults (SMD 4.89; CI 2.72,7.06, and SMD 8.40; CI 6.99,9.82, respectively). SF acts as a biomarker for pancreatic cancer, renal cell carcinoma, lung cancer, and head and neck cancer and is a sensitive biomarker for the detection of advanced stages of tumors.

Effect of different doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on cardiac parameters in male Wistar rats.

The objective of this study was to evaluate the effects of different doses of 2,4-dichlorophenoxyacetic herbicide in rat hearts. Exposure was through rat food that was nebulized with the herbicide. Thirty adult male Wistar rats (200-300 g) were used. The diet was exposed to 2,4-D in two different doses (CG: control group 10 ml distilled water; LCG: low concentration group 3.71 × 10-3 g.ia/ha diluted in 10 ml saline at 0.9% and HCG: High concentration group 9.28 × 10-3 g.ia/ha diluted in 10 ml 0.9% saline). After 6 months of exposure, blood samples were collected for CKMB evaluation, and left ventricular fragments were analyzed by histological evaluation, fibrosis measurements, fractal dimension and immunohistochemistry (BAX, Bcl2, TNF-α and NF-kB). There were no significant changes in CK-MB concentration, histological parameters, fibrosis measurements and fractal dimension. Long-term oral consumption of food nebulized by the herbicide 2,4-D promoted an increase in BAX, Bcl-2/BAX, and cytoplasmic NF-kB in the nuclear area of the group that received the highest dose of the herbicide. This suggests that the herbicide induces cardiotoxicity.

Fractal analysis and histomolecular phenotyping provides insights into extracellular matrix remodeling in the developing bovine fetal ovary.

Although studies have focused on extracellular matrix (ECM) remodeling during the formation and functioning of adult ovaries, there is no comprehensive understanding of the mechanisms controlling preantral follicle development in fetal bovine ovaries during gestation. Thus, to gain insights into ECM remodeling during initial ovarian development, we used fetal ovaries to quantify the fractal dimension (FD), total collagen, and relative mRNA abundance of genes related to ECM remodeling (COL1A1, COL1A2, COL4A1, MMP2, MMP9, MMP14, TIMP1, and TIMP2). For this, pairs of fetal ovaries were obtained from cows in a local abattoir at days 60, 90, 120, and 150 of gestation; one of each pair was submitted to RNA extraction for target transcript analysis, and the other was used for total collagen and FD evaluation. From day 120 total collagen appeared to occupy a greater area in the fetal ovary. The fractal analysis with picrosirius red staining shows higher at day 150 when compared with that on day 60. On the contrary, we found an inverse pattern when we used the hematoxylin and eosin staining approach. Concerning target gene expression, the relative abundances of COL1A1, COL4A1, MMP2, MMP14, TIMP1, and TIMP2 mRNA were higher on day 150 when compared with that on day 60. We conclude that fractal analysis reflects the morphological changes occurring during structural organization of the fetal ovary and that the expression of genes related to ECM remodeling is modulated throughout gestation in bovine fetal ovaries.

Bisphenol A Exposure Impairs Epididymal Development during the Peripubertal Period of Rats: Inflammatory Profile and Tissue Changes.

Bisphenol A (BPA) is a synthetic non-steroidal oestrogen used in the production of plastics. BPA can cause alterations in the endocrine system of human beings and animals at varied stages of development. During puberty, altered morphological, sexual behaviour and completion of the epididymal development occur. Therefore, this study aimed to evaluate the effects of BPA on epididymal development during the peripubertal period of rats. Male Wistar rats were treated with BPA via gavage at doses of 20 µg/kg or 200 µg/kg per day [post-natal day (PND] 36-66). The control group received the vehicles under the same conditions. Feed and water were provided ad libitum. On PND 67, the epididymis was removed, weighed, divided into caput/corpus and cauda sections. It was then used for sperm count determination; histopathological and stereological evaluation; inflammatory cell enzymatic profiling (myeloperoxidase activity - MPO; N-acetylglucosaminidase - NAG); immunohistochemistry for IL-6; and evaluation of superoxide anion levels and malondialdehyde (MDA). Exposure to BPA at 200 µg/kg caused a significant increase of MPO activity and immunoreactivity to IL-6 (interleukin-6) as well as remodelling of tissue components in the caput/corpus and cauda regions of the epididymis. Under these experimental conditions, it is concluded that BPA alters post-natal epididymal development.