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(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1477-7827-11-29 http://hdl.handle.net/11449/75090 |
Resumo: | 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. |
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NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferensAndrogen receptorsApoptosisH2 receptorsMorphometryNF-kappaBVas deferensandrogen receptorcimetidineformaldehydehycimetimmunoglobulin enhancer binding proteinparaffinsodium chlorideunclassified druganimal cellantibody labelingapoptosisbasal cellcell deathcontrolled studyepithelium cellgene overexpressionimmunohistochemistrymalemuscle cellnick end labelingnonhumanratsmooth muscle fibertransmission electron microscopytreatment durationvas deferensAnimalsCimetidineCollagenCytoplasmEpitheliumHistamine H2 AntagonistsImmunohistochemistryIn Situ Nick-End LabelingMaleMicroscopy, Electron, TransmissionMuscle, SmoothNF-kappa BRatsReceptors, AndrogenVas DeferensAnimaliaMyoidaRattusBackground: 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 PaulistaDepartment of Morphology and Genetics Federal University of São Paulo (UNIFESP), São Paulo/SPDepartment of Morphology Laboratory of Histology and Embryology Araraquara Dental School-UNESP Univ. Estadual PaulistaUniversidade Estadual Paulista (Unesp)Universidade Federal de São Paulo (UNIFESP)Koshimizu, Juliana Y. [UNESP]Beltrame, Flávia L.Pizzol, José P. de [UNESP]Cerri, Paulo Sérgio [UNESP]Caneguim, Breno H. [UNESP]Cerri, Estela Sasso [UNESP]2014-05-27T11:28:54Z2014-05-27T11:28:54Z2013-04-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/1477-7827-11-29Reproductive Biology and Endocrinology, v. 11, n. 1, 2013.1477-7827http://hdl.handle.net/11449/7509010.1186/1477-7827-11-29WOS:0003224017000012-s2.0-848758994552-s2.0-84875899455.pdf327849591120788244556300768413020000-0001-5756-5828Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengReproductive Biology and Endocrinology2.8521,203info:eu-repo/semantics/openAccess2024-01-10T06:28:26Zoai:repositorio.unesp.br:11449/75090Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:38:42.524247Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
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 |
title |
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 |
spellingShingle |
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 Koshimizu, Juliana Y. [UNESP] Androgen receptors Apoptosis H2 receptors Morphometry NF-kappaB Vas deferens androgen receptor cimetidine formaldehyde hycimet immunoglobulin enhancer binding protein paraffin sodium chloride unclassified drug animal cell antibody labeling apoptosis basal cell cell death controlled study epithelium cell gene overexpression immunohistochemistry male muscle cell nick end labeling nonhuman rat smooth muscle fiber transmission electron microscopy treatment duration vas deferens Animals Cimetidine Collagen Cytoplasm Epithelium Histamine H2 Antagonists Immunohistochemistry In Situ Nick-End Labeling Male Microscopy, Electron, Transmission Muscle, Smooth NF-kappa B Rats Receptors, Androgen Vas Deferens Animalia Myoida Rattus |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
author |
Koshimizu, Juliana Y. [UNESP] |
author_facet |
Koshimizu, Juliana Y. [UNESP] Beltrame, Flávia L. Pizzol, José P. de [UNESP] Cerri, Paulo Sérgio [UNESP] Caneguim, Breno H. [UNESP] Cerri, Estela Sasso [UNESP] |
author_role |
author |
author2 |
Beltrame, Flávia L. Pizzol, José P. de [UNESP] Cerri, Paulo Sérgio [UNESP] Caneguim, Breno H. [UNESP] Cerri, Estela Sasso [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Koshimizu, Juliana Y. [UNESP] Beltrame, Flávia L. Pizzol, José P. de [UNESP] Cerri, Paulo Sérgio [UNESP] Caneguim, Breno H. [UNESP] Cerri, Estela Sasso [UNESP] |
dc.subject.por.fl_str_mv |
Androgen receptors Apoptosis H2 receptors Morphometry NF-kappaB Vas deferens androgen receptor cimetidine formaldehyde hycimet immunoglobulin enhancer binding protein paraffin sodium chloride unclassified drug animal cell antibody labeling apoptosis basal cell cell death controlled study epithelium cell gene overexpression immunohistochemistry male muscle cell nick end labeling nonhuman rat smooth muscle fiber transmission electron microscopy treatment duration vas deferens Animals Cimetidine Collagen Cytoplasm Epithelium Histamine H2 Antagonists Immunohistochemistry In Situ Nick-End Labeling Male Microscopy, Electron, Transmission Muscle, Smooth NF-kappa B Rats Receptors, Androgen Vas Deferens Animalia Myoida Rattus |
topic |
Androgen receptors Apoptosis H2 receptors Morphometry NF-kappaB Vas deferens androgen receptor cimetidine formaldehyde hycimet immunoglobulin enhancer binding protein paraffin sodium chloride unclassified drug animal cell antibody labeling apoptosis basal cell cell death controlled study epithelium cell gene overexpression immunohistochemistry male muscle cell nick end labeling nonhuman rat smooth muscle fiber transmission electron microscopy treatment duration vas deferens Animals Cimetidine Collagen Cytoplasm Epithelium Histamine H2 Antagonists Immunohistochemistry In Situ Nick-End Labeling Male Microscopy, Electron, Transmission Muscle, Smooth NF-kappa B Rats Receptors, Androgen Vas Deferens Animalia Myoida Rattus |
description |
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. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-04-09 2014-05-27T11:28:54Z 2014-05-27T11:28:54Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1477-7827-11-29 Reproductive Biology and Endocrinology, v. 11, n. 1, 2013. 1477-7827 http://hdl.handle.net/11449/75090 10.1186/1477-7827-11-29 WOS:000322401700001 2-s2.0-84875899455 2-s2.0-84875899455.pdf 3278495911207882 4455630076841302 0000-0001-5756-5828 |
url |
http://dx.doi.org/10.1186/1477-7827-11-29 http://hdl.handle.net/11449/75090 |
identifier_str_mv |
Reproductive Biology and Endocrinology, v. 11, n. 1, 2013. 1477-7827 10.1186/1477-7827-11-29 WOS:000322401700001 2-s2.0-84875899455 2-s2.0-84875899455.pdf 3278495911207882 4455630076841302 0000-0001-5756-5828 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Reproductive Biology and Endocrinology 2.852 1,203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129446023004160 |