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1.
Reprod Toxicol ; 89: 136-144, 2019 10.
Article in English | MEDLINE | ID: mdl-31310804

ABSTRACT

Arsenic is a widely dispersed chemical compound in the environment and has been associated with the development of some diseases and different types of cancer. Little is known about the action of arsenic compounds on prostate development during prepuberty and puberty. This study evaluated prostate morphophysiology after sodium arsenite exposure during prepubertal period in rats. Male Wistar rats at PND23 were randomly distributed into three experimental groups (n = 10/group). The Ctrl group (filtered drinking water); As1 group (0.01 mg/L of NaAsO2); As2 group (10.0 mg/L of NaAsO2) that received the diluted solution in drinking water from PND23 to PND53. Histological and molecular analyzes showed developmental delay in the As1 group and important morphophysiological alterations in As2 group. The results showed that exposure to NaAsO2 during prepuberty compromised structural and functional maturation of the prostate in pubertal rats at both doses evaluated in this study.


Subject(s)
Aging/drug effects , Arsenites/toxicity , Environmental Pollutants/toxicity , Prostate/drug effects , Sexual Maturation/drug effects , Sodium Compounds/toxicity , Animals , Antioxidants/metabolism , Collagen/metabolism , Lipid Peroxidation/drug effects , Male , Prostate/growth & development , Prostate/metabolism , Prostate/pathology , Rats , Rats, Wistar , Testosterone/blood
2.
J Pharm Pharmacol ; 71(7): 1065-1071, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30919959

ABSTRACT

OBJECTIVES: This study evaluated raloxifene (ral) effects on LNCaP prostate tumour cells modulating the activity of GPER1/GPR30 receptors. METHODS: LNCaP cells were submitted for 40/120 min and 12 h to the following treatments: C: RPMI + DMSO; R: RPMI + Ral; G: RPMI + Ral + G15 (GPER1 antagonist). Trypan blue staining measured cell viability. Migratory potential (12 h) was measured by transwell migration test in translucent inserts, which were then stained with DAPI and analysed under a fluorescence microscope for quantification. Cells from 40- and 120-min treatments were subjected to protein extraction to the study of AKT, pAKT, ERK, pERK, ERß and SIRT1. KEY FINDINGS: There is a reduction in cellular viability in R compared to C at all evaluated times, and an increased cell viability in G when compared to R; cell viability was similar in C and G in all times studied. The migration assay demonstrated a significant decrease in migration potential of tumour cells in R compared to C and G. Ral treatment reduced pERK expression and increased pAKT in the treated groups after 40 min, pointing out to an antiproliferative and apoptotic effect in the GPER1-controlled rapid-effect pathways. CONCLUSIONS: Raloxifene was able to modulate GPER1 in LNCaP prostate tumour cells, decreasing cell viability and their migratory potential.


Subject(s)
Cell Movement/drug effects , Cell Survival/drug effects , MAP Kinase Signaling System/drug effects , Prostatic Neoplasms/drug therapy , Raloxifene Hydrochloride/pharmacology , Receptors, Estrogen/metabolism , Receptors, G-Protein-Coupled/metabolism , Cell Line, Tumor , Humans , Male , Middle Aged , Prostate/drug effects , Prostate/metabolism , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt , Signal Transduction
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