NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens
| Autor: | Flávia L. Beltrame, Estela Sasso-Cerri, Jose Paulo de Pizzol, Juliana Y Koshimizu, Breno Henrique Caneguim, Paulo Sérgio Cerri |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade Federal de São Paulo (UNIFESP) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Cytoplasm Apoptosis animal cell basal cell paraffin Epithelium Muscular layer chemistry.chemical_compound Endocrinology Vas Deferens androgen receptor Myocyte NF-kappaB rat hycimet Vas deferens NF-kappa B Obstetrics and Gynecology cimetidine muscle cell Immunohistochemistry unclassified drug medicine.anatomical_structure immunoglobulin enhancer binding protein cell death Histamine H2 Antagonists Receptors Androgen sodium chloride Collagen Cimetidine Histamine antibody labeling H2 receptors Programmed cell death medicine.medical_specialty gene overexpression nick end labeling Biology Androgen receptors Microscopy Electron Transmission Internal medicine transmission electron microscopy medicine In Situ Nick-End Labeling Animals Animalia controlled study nonhuman treatment duration Rattus Research Morphometry Muscle Smooth Rats Androgen receptor Reproductive Medicine chemistry Myoida smooth muscle fiber formaldehyde epithelium cell Pyknosis Developmental Biology |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Reproductive Biology and Endocrinology : RB&E |
| Popis: | Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:54Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:37:27Z : No. of bitstreams: 1 2-s2.0-84875899455.pdf: 3515438 bytes, checksum: bcbb303312508bf21ce057f018240a02 (MD5) Made available in DSpace on 2014-05-27T11:28:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-04-09 Background: Cimetidine, histamine H2 receptors antagonist, has caused adverse effects on the male hormones and reproductive tract due to its antiandrogenic effect. In the testes, peritubular myoid cells and muscle vascular cells death has been associated to seminiferous tubules and testicular microvascularization damages, respectively. Either androgen or histamine H2 receptors have been detected in the mucosa and smooth muscular layer of vas deferens. Thus, the effect of cimetidine on this androgen and histamine-dependent muscular duct was morphologically evaluated.Methods: The animals from cimetidine group (CMTG; n=5) received intraperitoneal injections of 100 mg/kg b.w. of cimetidine for 50 days; the control group (CG) received saline solution. The distal portions of vas deferens were fixed in formaldehyde and embedded in paraffin. Massońs trichrome-stained sections were subjected to morphological and the following morphometrical analyzes: epithelial perimeter and area of the smooth muscular layer. TUNEL (Terminal deoxynucleotidyl-transferase mediated dUTP Nick End Labeling) method, NF-kB (nuclear factor kappa B) and AR (androgen receptors) immunohistochemical detection were also carried out. The birefringent collagen of the muscular layer was quantified in picrosirius red-stained sections under polarized light. The muscular layer was also evaluated under Transmission Electron Microscopy (TEM).Results: In CMTG, the mucosa of vas deferens was intensely folded; the epithelial cells showed numerous pyknotic nuclei and the epithelial perimeter and the area of the muscular layer decreased significantly. Numerous TUNEL-labeled nuclei were found either in the epithelial cells, mainly basal cells, or in the smooth muscle cells which also showed typical features of apoptosis under TEM. While an enhanced NF-kB immunoexpression was found in the cytoplasm of muscle cells, a weak AR immunolabeling was detected in these cells. In CMTG, no significant difference was observed in the birefringent collagen content of the muscular layer in comparison to CG.Conclusions: Cimetidine induces significant damages in the epithelium; a possible antiandrogenic effect on the basal cells turnover should be considered. The cimetidine-induced muscle cells apoptosis confirms the susceptibility of these cells to this drug. The parallelism between enhanced cytoplasmic NF-kB immunolabeling in the damaged muscular tissue and muscle cell apoptosis suggests that this drug may avoid the translocation of NF-kB to the nucleus and interfere in the control of NF-kB-mediated smooth muscle cell apoptosis. The decreased immunoexpression of ARs verified in the damaged muscular tissue reinforces this possibility. © 2013 Koshimizu et al.; licensee BioMed Central Ltd. Department of Morphology Laboratory of Histology and Embryology Araraquara Dental School-UNESP Univ. Estadual Paulista Department of Morphology and Genetics Federal University of São Paulo (UNIFESP), São Paulo/SP Department of Morphology Laboratory of Histology and Embryology Araraquara Dental School-UNESP Univ. Estadual Paulista |
| Databáze: | OpenAIRE |
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