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1.
Chemosphere ; 363: 142895, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067823

RESUMO

Glyphosate-based herbicides (GBHs) are considered endocrine disruptors that affect the female reproductive tract of rats and ewe lambs. The present study aimed to investigate the impact of neonatal exposure to a low dose of a GBH on the ovarian follicular reserve of ewe lambs and the response to a gonadotropic stimulus with porcine FSH (pFSH). To this end, ewe lambs were orally exposed to an environmentally relevant GBH dose (1 mg/kg/day) or vehicle (Control) from postnatal day (PND) 1 to PND14, and then some received pFSH (50 mg/day) between PND41 and 43. The ovaries were dissected, and follicular types and gene expression were assessed via RT-PCR. The treatments did not affect the body weight of animals, but pFSH increased ovarian weight, not observed in GBH-exposed lambs. GBH-exposed lambs showed decreased Estrogen receptor-alpha (56%), Progesterone receptor (75%), Activin receptor II (ACVRII) (85%), and Bone morphogenetic protein 15 (BMP15) (88%) mRNA levels. Control lambs treated with pFSH exhibited downregulation of Follistatin (81%), ACVRII (77%), BMP15 (93%), and FSH receptor (FSHr) (72%). GBH-exposed lambs treated with pFSH displayed reduced ACVRII (68%), BMP15 (81%), and FSHr (50%). GBH-exposed lambs also exhibited decreased Anti-Müllerian hormone expression in primordial and antral follicles (27%) and (54%) respectively) and reduced Bone morphogenetic protein 4 (31%) expression in primordial follicles. Results suggest that GBH disrupts key follicular development molecules and interferes with pFSH action in ovarian receptors, decreasing the ovarian reserve. Future studies should explore whether this decreased ovarian reserve impairs adult ovarian function and its response to superovulation stimuli.


Assuntos
Glicina , Glifosato , Herbicidas , Reserva Ovariana , Ovário , Animais , Feminino , Herbicidas/toxicidade , Ovinos/fisiologia , Glicina/análogos & derivados , Glicina/toxicidade , Ovário/efeitos dos fármacos , Reserva Ovariana/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Folículo Ovariano/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue
2.
Environ Pollut ; 296: 118729, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34953950

RESUMO

Glyphosate-based herbicides (GBHs) are the agrochemicals most used around the globe. However, they might have adverse effects on human and animal health. Previously, we showed that female rats neonatally exposed to GBHs exhibit altered expression of morphogenetic molecules and biomarkers of uterine development. We also observed a reduction in the size of implantation sites, altered expression of decidualization-related molecules, and increased post-implantation losses. Since decidualization comprises morphogenetic, biochemical and vascular changes, here we investigated the effects of neonatal GBH exposure on uterine angiogenesis in neonatal and pregnant rats. To achieve this, Wistar female rats were exposed to saline solution or GBH (2 mg glyphosate/kg-bw/day) on post-natal days (PND) 1, 3, 5 and 7. On PND8, uterine samples were collected for developmental studies. On PND90, the remaining females were mated and in the morning of gestational day (GD) 9, the implantation sites were collected. Angiogenesis-related molecules and cells involved in this process were identified and/or measured by immunohistochemistry or RT-PCR. On PND8, GBH-treated rats showed increased vascular endothelial growth factor (VEGF) expression and decreased Notch1, inducible nitric oxide synthase (iNOS) and Angiopoietin-2 (Ang2) mRNA levels. Vascular area, vessel diameter, endothelial cell proliferation, VEGF and Nestin protein expression, and VEGF, Notch1, iNOS and cyclooxygenase-2 (Cox-2) genes were downregulated in implantation sites of exposed females, while Ang2, VEGF receptor 1 and interleukin-10 (IL-10) were increased. Mast cells and macrophages were increased on PND8 and GD9 of treated rats. The increased Transforming growth factor-beta expression in the antimesometrial zone and IL-10 mRNA expression suggest that the M2 type is the predominant population of macrophages on implantation sites. In conclusion, neonatal GBH exposure alters the expression of angiogenesis-related molecules at neonatal uterine development and decidual reaction, suggesting altered vascular support. These alterations might contribute to the increased post-implantation losses observed in GBH-treated rats.


Assuntos
Herbicidas , Animais , Feminino , Glicina/análogos & derivados , Glicina/toxicidade , Herbicidas/toxicidade , Gravidez , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular , Glifosato
3.
Food Chem Toxicol ; 134: 110832, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31550491

RESUMO

Endosulfan and glyphosate are widely used pesticides and have been associated to reproductive disorders. We examine the acute and long-term effects of postnatal exposure to commercial formulations of endosulfan (EF), glyphosate (glyphosate-based herbicide, GBH) and a mixture of both pesticides (MIX). After birth, female pups of Wistar rats received saline solution (CONTROL), EF (600 µg/kg of b.w/day), GBH (2 mg/kg of b.w/day) or a mixture (at the same doses) from postnatal day (PND) 1 to PND7. The uterine histology and expression of Hoxa10, estrogen (ERα) and progesterone (PR) receptors were evaluated on PND8. Reproductive performance was evaluated on gestational day 19. GBH and MIX rats showed an increment of 1) the incidence of luminal epithelial hyperplasia, 2) PR and Hoxa10 expression. EF modified ERα and Hoxa10 expression. During adulthood, MIX and GBH rats showed higher post-implantation losses while EF alone produced an increase of pre-implantation losses. We showed that the co-administration of both pesticides produced acute uterine effects and long-term deleterious reproductive effects that were similar to those induced by GBH alone. We consider important to highlight the necessity to evaluate the commercial pesticide mixture as a more representative model of human exposure to a high number of pesticides.


Assuntos
Endossulfano/toxicidade , Glicina/análogos & derivados , Herbicidas/toxicidade , Inseticidas/toxicidade , Útero/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Feminino , Glicina/toxicidade , Proteínas/metabolismo , Ratos , Ratos Wistar , Útero/anatomia & histologia , Útero/metabolismo , Glifosato
4.
Food Chem Toxicol ; 118: 111-118, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29746933

RESUMO

Our aim was to evaluate whether postnatal exposure to a glyphosate-based herbicide (GBH) modifies mammary gland development in pre- and post-pubertal male rats. From postnatal day 1 (PND1) to PND7, male rats were injected subcutaneously every 48 h with either saline solution (vehicle) or 2 mg GBH/kg·bw. On PND21 and PND60, mammary gland and blood samples were collected. Estradiol (E2) and testosterone (T) serum levels, mammary gland histology, collagen fiber organization, mast cell infiltration, proliferation index, and estrogen (ESR1) and androgen receptor (AR) expression levels were evaluated. At PND21, GBH-exposed male rats exhibited greater development of the mammary gland with increased stromal collagen organization and terminal end buds (TEBs) compared to control rats. At PND60, the number of TEBs remained high and was accompanied by an increase in mast cell infiltration, proliferation and ESR1 expression in GBH-exposed male rats. In contrast, no effects were observed in E2 and T serum levels and AR expression in both days studied. Our results showed that a postnatal subacute treatment with GBH induces endocrine-disrupting effects in the male mammary gland in vivo, altering its normal development.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Proliferação de Células , Estradiol/sangue , Receptor alfa de Estrogênio/metabolismo , Feminino , Glicina/toxicidade , Masculino , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Mastócitos/citologia , Ratos Wistar , Receptores Androgênicos/metabolismo , Maturidade Sexual , Testosterona/sangue , Testes de Toxicidade Subaguda , Glifosato
5.
Reprod Toxicol ; 73: 87-95, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28780397

RESUMO

We investigated whether defective modulation of uterine signaling may cause decidualization failure in rats neonatally exposed to a glyphosate-based herbicide (GBH). Female pups received vehicle or 2mg/kg of GBH from postnatal day (PND) 1 to PND7. On PND8 and PND21, Wnt5a and ß-catenin expression was evaluated in uterine samples. On gestational day (GD) 9, Wnt5a, Wnt7a and ß-catenin expression and Dkk1 and sFRP4 mRNA were evaluated on implantation sites. On PND8, GBH-exposed rats showed increased Wnt5a and ß-catenin expression in luminal epithelium (LE), whereas on PND21, they showed increased Wnt5a and ß-catenin expression in subepithelial stroma but decreased ß-catenin expression in glandular epithelium. On GD9, GBH-exposed rats showed decreased Wnt5a and Wnt7a expression in the antimesometrial zone and LE respectively, without changes in ß-catenin expression, while Dkk1 and sFRP4 were up- and down-regulated respectively. We concluded that neonatal GBH exposure may lead to embryo losses by disturbing uterine signaling.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Útero/efeitos dos fármacos , Animais , Feminino , Glicina/toxicidade , Peptídeos e Proteínas de Sinalização Intercelular/genética , Troca Materno-Fetal , Gravidez , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Ratos Wistar , Proteínas Ribossômicas/genética , Transdução de Sinais/efeitos dos fármacos , Útero/metabolismo , Proteínas Wnt/metabolismo , Proteína Wnt-5a/metabolismo , beta Catenina/metabolismo , Glifosato
6.
Toxicology ; 376: 2-14, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27287056

RESUMO

Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. No reports are available regarding the effects of GBHs exposure on uterine development. We evaluated if neonatal exposure to a GBH affects uterine morphology, proliferation and expression of proteins that regulate uterine organogenetic differentiation in rats. Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2mg/kg) by sc injection every 48h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic differentiation. PR and Hoxa10 were deregulated both immediately and two weeks after the exposure. ERα was induced in the stromal compartment on PND8, and was downregulated in the luminal epithelial cells of gyphosate-exposed animals on PND21. GBH treatment also increased the expression of Wnt7a in the stromal and glandular epithelial cells on PND21. Neonatal exposure to GBH disrupts the postnatal uterine development at the neonatal and prepubertal period. All these changes may alter the functional differentiation of the uterus, affecting the female fertility and/or promoting the development of neoplasias.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Útero/efeitos dos fármacos , Útero/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Feminino , Glicina/toxicidade , Gravidez , Distribuição Aleatória , Ratos , Ratos Wistar , Útero/metabolismo , Glifosato
7.
Environ Toxicol ; 32(4): 1191-1201, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27463640

RESUMO

Glyphosate is the active ingredient of several herbicide formulations. Different reports suggest that glyphosate-based herbicides (GBHs) may act as endocrine disruptors. We evaluated the potential estrogenic effects of a GBH formulation using the uterotrophic assay. Adult ovariectomized rats were sc injected for 3 consecutive days with: saline solution (vehicle control), 2.10-5  g E2 /kg/day (uterotrophic dose; UE2 ), 2.10-7  g E2 /kg/day (nonuterotrophic dose; NUE2 ), or 0.5, 5, or 50 mg GBH/kg/day of the. Twenty-four hours after the last injection, the uterus was removed and weighed and processed for histopathology and mRNA extraction. Epithelial cell proliferation and height and expression of estrogen-responsive genes were evaluated (estrogen receptors, ERα and ERß; progesterone receptor, PR; complement 3, C3). Uterine weight and epithelial proliferation were not affected by GBH. However, the luminal epithelial cell height increased at GBH0.5. ERα mRNA was downregulated by all GBH doses and E2 groups, whereas PR and C3 mRNA were diminished by GBH0.5. GBH5-, GBH50-, and UE2 -treated rats showed downregulated ERα protein expression in luminal epithelial cells, while the receptor was upregulated in the stroma. GBH upregulated ERß (GBH0.5-50) and PR (GBH5) expressions in glandular epithelial cells, similar effect to that of NUE2 group. These results indicate that, although the uterine weight was not affected, GBH modulates the expression of estrogen-sensitive genes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1191-1201, 2017.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Útero/efeitos dos fármacos , Animais , Animais Endogâmicos , Estradiol/fisiologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Glicina/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Wistar , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Útero/metabolismo , Útero/patologia , Glifosato
8.
Reproduction ; 152(5): 403-15, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27486271

RESUMO

In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Reprodução/fisiologia , Animais , Animais Recém-Nascidos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Decídua/efeitos dos fármacos , Decídua/crescimento & desenvolvimento , Endométrio/efeitos dos fármacos , Endométrio/crescimento & desenvolvimento , Feminino , Glicina/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Reprodução/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/crescimento & desenvolvimento , Glifosato
9.
Mol Cell Endocrinol ; 425: 37-47, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26911934

RESUMO

Neonatal exposure to a low dose of endosulfan may disrupt the expression of Wnt7a and ß-catenin during uterine development leading to the failure of uterine functional differentiation during implantation. New-born female Wistar rats were treated with vehicle, endosulfan (600 µg/kg/d, E600) or diethylstilbestrol (0.2 µg/kg/d, DES) on postnatal days (PNDs) 1, 3, 5 and 7. Subsequently, uterine histomorphology and the protein expression of Wnt7a and ß-catenin were evaluated on PND8, PND21 and gestational day (GD) 5 (pre-implantation period). In the E600 rats, Wnt7a and ß-catenin protein expression was increased in the epithelium on PND8, and Wnt7a expression was decreased in the endometrial glands on PND21. On GD5, the number of uterine glands was decreased in the E600-and DES-treated rats. In addition, Wnt7a expression was decreased in all uterine compartments, and ß-catenin expression was increased in the luminal and glandular epithelia of the E600-and DES-treated rats. Disruption of Wnt7a and ß-catenin uterine expression in the prepubertal and adult females altered the uterine preparation for embryo implantation, which could be associated with the subfertility triggered by endosulfan.


Assuntos
Endossulfano/efeitos adversos , Proteínas Proto-Oncogênicas/metabolismo , Útero/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Dietilestilbestrol/toxicidade , Endossulfano/administração & dosagem , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Ratos , Ratos Wistar , Útero/crescimento & desenvolvimento , Útero/metabolismo
10.
J Cell Biochem ; 114(3): 669-80, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23059845

RESUMO

Increased expression of COX-2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX-2 protects hepatocytes from several pro-apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX-2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain wild type (Wt) and transgenic in COX-2 (hCOX-2 Tg) were separated into Control (vehicle) and SID (streptozotocin induced diabetes, 200 mg/kg body weight, i.p.). Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. This situation was improved in diabetic COX-2 Tg. In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. Pro-apoptotic state in the liver of diabetic animals was improved by over-expression of COX-2. We also analyzed the roles of high glucose-induced apoptosis and hCOX-2 in vitro. Non-transfected and hCOX-2-transfected cells were cultured at 5 and 25 mM of glucose by 72 h. At 25 mM there was an increase in apoptosis in non-transfected cells versus those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX-2-transfected cells was suppressed by addition of DFU (COX-2 selective inhibitor), and mimicked by addition of PGE(2) in non-transfected cells. Taken together, these results demonstrate that hyperglycemia-induced hepatic apoptosis is protected by hCOX-2 expression.


Assuntos
Apoptose , Ciclo-Oxigenase 2/metabolismo , Hiperglicemia/metabolismo , Fígado/metabolismo , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Ciclo-Oxigenase 2/genética , Citocromos c/biossíntese , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/biossíntese , Fígado/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Estreptozocina , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/biossíntese , Proteína X Associada a bcl-2/biossíntese , Proteína de Morte Celular Associada a bcl/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese
11.
Mol Immunol ; 48(12-13): 1397-407, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21481476

RESUMO

We analyzed the contribution of TNF-α intracellular pathway in the development of apoptosis in the liver of streptozotocin-induced diabetic rats. In liver tissue, diabetes promoted a significant increase of TNF-α/TNF-R1, and led to the activation of caspase-8, of nuclear factor kappa B (NFκB), and JNK signaling pathways. The activation of NFκB led to an induction of iNOS and consequent increase in NO production. As a consequence of such changes a significant increase of caspase-3 activity and of apoptotic index were observed in the liver of diabetic animals. Importantly, the treatment in vivo of diabetic rats with etanercept (TNF-α blocking antibody) or aminoguanidine (selective iNOS inhibitor) significantly attenuated the induction of apoptosis by reduction of caspase-3 activity. Overall, we demonstrated that in the diabetes enhances TNF-α in the liver, which may be a fundamental key leading to apoptotic cell death, through activation of caspase-8, NFκB and JNK pathways.


Assuntos
Apoptose , Diabetes Mellitus Tipo 1/metabolismo , Fígado/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Western Blotting , Caspase 3/metabolismo , Caspase 8/metabolismo , Inibidores de Caspase , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1/patologia , Espectroscopia de Ressonância de Spin Eletrônica , Etanercepte , Guanidinas/farmacologia , Imunoglobulina G/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/patologia , Masculino , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Receptores do Fator de Necrose Tumoral , Transdução de Sinais , Estreptozocina
12.
Cytokine ; 49(1): 64-72, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19892564

RESUMO

Trypanosoma cruzi (T. cruzi) infected C57BL/6 mice developed a progressive fatal disease due to an imbalance in the profile of circulating related compounds accompanying infection like tumor necrosis factor alpha (TNFalpha). TNFalpha has been proposed as an important effector molecule in apoptosis. In this work, we evaluate inflammation and the proteins involved in apoptotic process in liver of infected mice and the role of TNFalpha. C57BL6/mice were infected subcutaneously with 100 viable trypomastigotes of Tulahuén strain of T cruzi. One set of these animals were treated with 375 microg of antihuman TNFalpha blocking antibody. Animals were sacrificed at 14 days post-infection (p.i).The analyses of Bcl-2 family proteins revealed an increase of the pro-apoptotic proteins Bax and tBid in T. cruzi-infected mice. Compared with control animals, cytochrome c release was increased. Apoptosis was also induced in infected mice. Anti-TNFalpha treatment decreases hepatic apoptosis. Our results suggest that T. cruzi infection induces programmed cell death in the host liver by increase of TNFalpha production, associated with TNF-R1 over-expression, that set in motion the Bid cleavage and mitochondrial translocation, Bax mitochondrial translocation, cytochrome c release, and ultimately apoptosis induction.


Assuntos
Morte Celular/imunologia , Doença de Chagas/imunologia , Inflamação , Fígado/imunologia , Fígado/parasitologia , Trypanosoma cruzi/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/imunologia , Citocromos c/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Inflamação/imunologia , Inflamação/microbiologia , Fígado/citologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/genética , Proteína X Associada a bcl-2/imunologia , Proteína bcl-X/imunologia
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