Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: Evidence for the testicular vasculature atrophy

Autor(es)

Beltrame, Flavia L. ^[1] ; Cerri, Paulo S. ^[2] ; Sasso-Cerri, Estela ^[2]

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo UNIFESP, Dept Morphol & Genet, Sao Paulo, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Dent, Lab Histol & Embryol, Dept Morphol, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: REPRODUCTIVE TOXICOLOGY; v. 57, p. 50-58, NOV 2015.
• Citações Web of Science: 7

Resumo

The antiulcer drug cimetidine has shown to cause changes in the testicular microvasculature of adult rats. Since Leydig cells (LCs) produce the pro-angiogenic factor, EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK-1), this study examined the effect that cimetidine might have on LCs in testes with damaged vasculature. Rats received intraperitoneal injections of 100 mg/kg of cimetidine (cimetidine group) or saline vehicle (control group) for 50 days. Serum testosterone levels were measured by chemiluminescence immunoassay and testicular sections were subjected to TUNEL and immunohistochemical reactions for caspase-3, 17 beta-HSD6, CD163 (ED2 macrophage), PK-1 and androgen receptor (AR). LCs in the cimetidine group showed TUNEL and caspase-3 positive labeling and apoptotic ultrastructural features. Moreover, the presence of 17 beta-HSD6-positive inclusions inside macrophages and the reduced number of LCs, AR immunoreactivity and serum testosterone levels correlated with a decrease in either the number of PK-1-immunostained LCs or PK-1 immunoreactivity. Although it is not clear which cell type is the primary target of cimetidine in the testicular interstitial compartment, these findings support a direct link between cimetidine-induced testicular vascular atrophy and LCs damage. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 10/02409-5 - Aspectos histopatológicos do tecido intersticial de ratos tratados com cimetidina e participação da vitamina B12 na reparação da espermatogênese
• Beneficiário: Flávia Luciana Beltrame
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 06/54776-6 - Avaliação morfológica e morfométrica de testículos de ratos tratados com cimetidina, com ênfase na célula de Sertoli e na vascularização intersticial
• Beneficiário: Estela Sasso Cerri
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/25322-0 - Efeito da cimetidina na histoarquitetura epididimária e avaliação do DNA espermático de ratos tratados com cimetidina e suplementados com vitamina B12
• Beneficiário: Flávia Luciana Beltrame
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/23845-3 - Avaliação do efeito da Vitamina B12 sobre as fases mitótica e meiótica da espermatogênese e sobre o DNA espermático de ratos tratados com cimetidina
• Beneficiário: Estela Sasso Cerri
• Modalidade de apoio: Auxílio à Pesquisa - Regular