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1.
IET Nanobiotechnol ; 15(5): 473-483, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34694755

RESUMO

This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-ß1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Nanopartículas , Óxido de Zinco , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Rim , Masculino , Ratos , Estreptozocina/toxicidade , Fator A de Crescimento do Endotélio Vascular
2.
Artigo em Inglês | MEDLINE | ID: mdl-33100210

RESUMO

BACKGROUND: Activation of the Angiotensin II type 1 receptor (AT1R) has been implicated in the pathogenesis of the cardiovascular disease, while activation of Angiotensin II type 2 receptor (AT2R) leads to effects that are opposite to those mediated by AT1R. The interaction between female sex hormones and the renin-angiotensin system was proven to play an essential role in the pathological changes in the cardiovascular system. OBJECTIVES: To investigate the direct effect of estrogen and progesterone on arterial and cardiac AT1R and AT2R expression in vivo in male. METHOD: Male adult rats were assigned into four groups: Group 1 (control), group 2 (progesterone treated group; 10mg/kg), group 3 (estrogen treated group; 20µg/kg) and group 4 (progesterone; 10mg/kg + estrogen; 20µg/kg treated group). All treatments were administrated subcutaneously every second day for 21days. RESULTS: Estrogen treatments increase the left ventricle (LV) protein expression of AT1R, and progesterone treatment decreased the LV protein expression of AT2R. In the aorta, estrogen treatment increased the mRNA expression levels of AT1R, while progesterone treatment increased the AT2R mRNA expression levels. Estrogen treatment decreases the LV and aortic endothelial nitric-oxide synthase (eNOS) mRNA levels while progesterone treatments decrease the LV eNOS mRNA levels but increase the aortic eNOS mRNA levels. The serum angiotensin II levels were increased by estrogen treatment only. CONCLUSION: Both estrogen and progesterone treatments appear to have a harmful effect on the male rat hearts, possibly by increasing the protein expression of AT1R (for estrogen), decrease the protein and mRNA expression of AT2R (for progesterone), and decrease the eNOS mRNA levels (for both). However, it seems that progesterone but not estrogen exerts a vascular protective effect in males.


Assuntos
Aorta/efeitos dos fármacos , Estrogênios/farmacologia , Coração/efeitos dos fármacos , Progesterona/farmacologia , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética , Animais , Aorta/metabolismo , Expressão Gênica/efeitos dos fármacos , Masculino , Miocárdio/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/metabolismo
3.
Drug Deliv Transl Res ; 10(1): 216-226, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31637677

RESUMO

Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor ß1 (TGF-ß1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.


Assuntos
Albuminúria/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Ouro/administração & dosagem , Podócitos/citologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Injeções Intraperitoneais , Masculino , Nanopartículas Metálicas , Estresse Oxidativo/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Ratos , Estreptozocina
4.
Phytother Res ; 31(12): 1910-1915, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28960541

RESUMO

This study addresses the possible protective effects of thymoquinone (TQ) against the development of experimentally-induced benign prostatic hyperplasia (BPH) in Wistar rats. Eighteen adult male rats were divided into three groups; the negative control group (n = 6) received vehicle, and two groups received subcutaneous testosterone injection (3 mg/kg). Animals receiving testosterone were randomized to untreated BPH group (n = 6) and BPH + TQ treated group (n = 6, 50 mg/kg orally for 14 days). Histological changes and the mRNA levels of transforming growth factor-ß1 (TGF-ß1 ) and vascular endothelial growth factor-A (VEGF-A) were analyzed. Additionally, dihydrotestosterone and interleukin-6 (IL-6) serum levels were determined. The presented research shows significant increases in prostate weight/body weight ratio, prostate epithelial thickness, serum IL-6 and dihydrotestosterone levels, and the prostatic expressions of TGF-ß1 and VEGF-A in the untreated BPH rats. Histological examination of the prostate tissues in the BPH rats showed an elevated level of proliferation in the stromal area and glandular epithelia with abundant intraluminal papillary folds. However, a reduction in prostate weight/body weight ratio, epithelial hyperplasia, serum IL-6 levels, and the expressions of TGF-ß1 and VEGF-A were observed in the BPH + TQ treated rats compared with the untreated BPH rats. The findings support TQ as a useful natural treatment for animal BPH model. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Benzoquinonas/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Testosterona/efeitos adversos , Animais , Benzoquinonas/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Wistar
5.
Folia Biol (Krakow) ; 55(1-2): 41-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17687933

RESUMO

In the premetamorphic larval green toad, B. viridis viridis, as in other anurans, the skin is made up of a fibrous dermis and an epidermis of stratified epithelium. The effects of bromocriptine, an antiprolactin drug, on the premetamorphic skin of B. viridis viridis was examined. Bromocriptine, dissolved in rearing water at four different concentrations, induced a number of changes in the skin of treated tadpoles. In rough sequence of appearance, these changes include: retraction ofthe melanocyte dendrites, synchronous burst ofthe apical vesicles of the superficial epithelial cells, gradual disappearance of the melanosomes from the epithelial cells and widening of the intercellular spaces. In addition, macrophages appeared in the superficial dermis amongst the retracted melanocytes. White crystals were observed on the skin surface and similar crystals were ingested by the macrophages. Prolonged treatment with bromocriptine resulted in hypertrophy and extraction of some epidermal cells. Deep melanocytes of the mesenteries were not affected by bromocriptine-treatment indicating that the drug did not penetrate deep into the tadpole tissue. Whether the macrophages observed in the dermis were recruited from deeper tissues or were converted melanocytes is another issue in need of study.


Assuntos
Bromocriptina/farmacologia , Bufonidae , Agonistas de Dopamina/farmacologia , Pele/efeitos dos fármacos , Animais , Larva , Microscopia Eletrônica , Pele/ultraestrutura
6.
Folia Biol (Krakow) ; 53(3-4): 179-81, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-19058540

RESUMO

The flank skin of the premetamorphic stage of the green toad, Bufo viridis viridis, was studied by transmission electron microscopy. The skin was typically larval amphibian, made up of a highly fibrous and vascular dermis to the inside and a highly cellular epidermis to the outside with a distinct basal lamina separating the two layers. The epidermis is three-cells thick. The epidermal cells, mostly keratinocytes, are closely packed together and are attached to each other through desmosomes and interdigitations. The basal keratinocytes are anchored to the basal lamina through hemidesmosomes. In addition to the keratinocytes, some other types of cells known in the amphibian larval skin were found. These cells include mucus-secreting, mitochondria-rich cells, Merkle cells and flask cells. Anew type of cells, the dark cells, are described in this paper. The dark cell rests on the basal lamina. It is a ramified cell with a number of cytoplasmic processes intervening in between the keratinocytes. The cytoplasm is strikingly dark and rich with polysomes and granular endoplasmic reticulum.


Assuntos
Bufonidae/fisiologia , Epiderme/ultraestrutura , Animais , Membrana Celular/ultraestrutura , Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Larva/fisiologia
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