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1.
Ultrastruct Pathol ; 48(1): 29-41, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37970647

RESUMO

Investigation the protective effect of transient receptor potential channel modulator 2-Aminoethoxydiphenyl Borate (2-APB) on aminoglycoside nephrotoxicity caused by reactive oxygen species, calcium-induced apoptosis and inflammation was aimed. Forty Wistar rats were divided (n=8) as follows: Control group; DMSO group; 2-APB group; Gentamicin group (injected 100 mg/kg gentamicin intramuscularly for 10 days); Gentamicin+ 2-APB group (injected 2 mg/kg 2-APB intraperitoneally, then after 30 minutes 100 mg/kg gentamicin was injected intramuscularly for 10 days). Blood samples were collected for biochemical analyses, kidney tissue samples were collected for light, electron microscopic and immunohistochemical investigations. In gentamicin group glomerular degeneration, tubular dilatation, vacuolization, desquamation of tubular cells and hyaline cast formation in luminal space and leukocyte infiltration were seen. Disorganization of microvilli of tubular cells, apical cytoplasmic blebbing, lipid accumulation, myelin figure like structure formation, increased lysosomes, mitochondrial swelling and disorganization of cristae structures, apoptotic changes and widening of intercellular space were found. TNF-α, IL-6 and caspase 3 expressions were increased. BUN and creatinine concentrations were increased. Increase in MDA levels and decrease in SOD activities were determined. Even though degeneration still continues in gentamicin+2-APB treatment group, severity and the area it occupied were decreased and the glomerular and tubule structures were generally preserved. TNF-α, IL-6, caspase 3 immunoreactivities and BUN, creatinine, MDA concentrations were reduced and SOD activities were increased markedly compared to gentamicin group. In conclusion, it has been considered that 2-APB can prevent gentamicin mediated nephrotoxicity with its anti-oxidant, anti-apoptotic and anti-inflammatory effects.


Assuntos
Nefropatias , Rim , Ratos , Animais , Caspase 3/metabolismo , Caspase 3/farmacologia , Aminoglicosídeos/efeitos adversos , Aminoglicosídeos/metabolismo , Ratos Wistar , Creatinina/metabolismo , Creatinina/farmacologia , Fator de Necrose Tumoral alfa , Interleucina-6 , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Antibacterianos/efeitos adversos , Antioxidantes/farmacologia , Gentamicinas/toxicidade , Gentamicinas/metabolismo , Superóxido Dismutase/metabolismo , Estresse Oxidativo
2.
Reprod Biol ; 20(1): 25-32, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924508

RESUMO

The aim of this study was to demonstrate the effects of vitamin D treatment on ultrastructural changes and AMHR2 expression in the ovary in PCOS rat model. A total of 24 female prepubertal rats were divided into 3 groups. In group 1, sesame oil was injected and used as control group. In group 2, PCOS was created by the injection of 6 mg/kg/day DHEA. In group 3, PCOS was created and 120 ng/100 g 1,25 (OH)2D3 treatment was performed. At the end of the 28th day, the blood samples were collected. The ovarian tissues were obtained for electron microscopic and immunohistochemical examinations. Serum AMH, testosterone, FSH, LH levels and LH/FSH ratios were higher in the PCOS group compared to the control group and decreased in the treatment group compared to the PCOS group. AMHR2 expression was increased in atretic and premature luteinizate antral follicles in the PCOS group compared to the control group, and decreased in the treatment group compared to the PCOS group. PCOS group electron micrographs showed degenerative changes in developing follicles, cystic follicles characterised with granulosa cell layer attenuation and thickening of the theca cell layer, and lipid accumulation in the interstitial cells. Structural changes observed in the PCOS group were improved with vitamin D treatment. As a result, there is an interaction between PCOS, AMH serum levels and AMHR2 in the ovarian follicles. Vitamin D has a positive effect on hormonal and structural changes in the PCOS group. We concluded that vitamin D supplementation may be beneficial in PCOS patients.


Assuntos
Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Animais , Hormônio Antimülleriano/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Ovário/metabolismo , Ovário/ultraestrutura , Síndrome do Ovário Policístico/sangue , Ratos Wistar , Vitamina D/farmacologia , Vitaminas/farmacologia
3.
Adv Clin Exp Med ; 28(3): 291-297, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29969202

RESUMO

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Propranolol/uso terapêutico , Sepse/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Ligadura , Pulmão/patologia , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
4.
Reprod Biol ; 18(1): 53-59, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29325695

RESUMO

In this study, we aimed to investigate the structural changes seen in the endometrium in experimental PCOS rat model and the effects of vitamin D treatment on these changes at immunohistochemical and electron microscopic levels. 24 prepubertal female rats were divided into three groups. Two groups were injected with dehydroepiandrosterone and one of them was treated with 1,25(OH)2 D3 at the same time. The control group was injected with sesame oil. At the end of the 28th day, the blood samples were collected. Uterus tissues were prepared for light and electron microscopic examinations. Epithelial, stromal and endometrial thickness measurements were investigated. Immunohistochemical staining was applied against caspase-3 and Ki-67. Serum AMH and estradiol levels were higher in PCOS group compared to the control group. Serum progesterone levels were similar in all groups. Endometrial, epithelial and stromal thickness measurements were increased in PCOS group compared to the control group, and decreased in the vitamin D treatment group compared to the PCOS group. Light and electron microscopic results of PCOS group showed an increase in apoptosis and proliferation. In the PCOS group, immunohistochemical staining of caspase-3 and Ki-67 were found to be higher than in the control group, but stainings were decreased with vitamin D treatment compared to PCOS group. Structural changes observed in endometrium may be related to implantation problems seen in patients with PCOS. Our studies suggest that vitamin D therapy may be beneficial in these patients.


Assuntos
Calcitriol/uso terapêutico , Modelos Animais de Doenças , Endométrio/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Células Estromais/efeitos dos fármacos , Útero/efeitos dos fármacos , Deficiência de Vitamina D/tratamento farmacológico , Animais , Hormônio Antimülleriano/sangue , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/metabolismo , Calcitriol/administração & dosagem , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/patologia , Endométrio/ultraestrutura , Estradiol/sangue , Feminino , Imuno-Histoquímica , Injeções Subcutâneas , Antígeno Ki-67/metabolismo , Microscopia Eletrônica de Transmissão , Tamanho do Órgão/efeitos dos fármacos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Progesterona/sangue , Ratos , Células Estromais/metabolismo , Células Estromais/patologia , Células Estromais/ultraestrutura , Útero/metabolismo , Útero/patologia , Útero/ultraestrutura , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/patologia
5.
Ultrastruct Pathol ; 42(1): 55-64, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29192811

RESUMO

AIM: The aim of this study was to investigate the effects of vitamin D treatment on ovary in experimentally designed polycystic ovary syndrome of female rats using light and electron microscopic techniques. METHODS: Twenty-four female pre-pubertal rats were divided into control, DHEA and DHEA+Vit.D groups. In DHEA group, the PCOS rat model was developed by 6mg/kg/day dehydroepiandrosterone administration as subcutaneously injections. In DHEA+Vit.D group, 6 mg/kg/day DHEA and 120ng/100g/week 1,25(OH)2D3 was performed simultaneously. Controls were injected with vehicle alone. At the end of the 28 days, blood samples were collected and the ovarian tissues were taken for histological examinations. RESULTS: FSH, LH levels, LH/FSH ratio, and testosterone levels showed a significant increase in DHEA group when compared with the control group. Moreover, these measurements were lower in the treatment group than the DHEA group. In DHEA group, increased number of atretic follicles and cystic follicles were seen with light microscopic analysis. Cystic follicles with attenuated granulosa cell layers and thickened theca cell layers and lipid accumulation in interstitial cells were observed by electron microscope. It is observed that atretic and cystic follicles were decreased as a result of vitamin D treatment. CONCLUSION: Our results indicate the curative role of vitamin D treatment on the androgen excess in PCOS rat model which causes abnormalities in ovarian morphology and functions. Vitamin D has positive effects on the hormonal and structural changes observed in PCOS, but it has been concluded that long-term use may be more beneficial.


Assuntos
Antioxidantes/farmacologia , Ovário/ultraestrutura , Síndrome do Ovário Policístico/patologia , Vitamina D/farmacologia , Animais , Desidroepiandrosterona/toxicidade , Modelos Animais de Doenças , Feminino , Microscopia Eletrônica de Transmissão , Ovário/efeitos dos fármacos , Ovário/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Ratos , Ratos Wistar
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