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1.
Sci Total Environ ; 751: 142269, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33182016

RESUMEN

This study presents a high-throughput (HTP) micronucleus assay in multi-well plates with an automated evaluation for risk assessment applications. The evaluation of genotoxicity via the micronucleus assays according to international guidelines ISO 21427-2 with Chinese hamster (Cricetulus griseus) V79 cells was the starting point to develop our methodology. A drawback of this assay is that it is very time consuming and cost intensive. Our HTP micronucleus assay in a 48-well plate format allows for the simultaneous assessment of five different sample-concentrations with additional positive, negative and solvent controls with six technical replicates each within a quarter of the time required for the equivalent evaluation using the traditional slide method. In accordance with the 3R principle, animal compounds should be replaced with animal-free alternatives. However, traditional cell culture-based methods still require animal derived compounds like rat-liver derived S9-fraction, which is used to simulate the mammalian metabolism in in vitro assays that do show intrinsic metabolization capabilities. In the present study, a recently developed animal-free biotechnological alternative (ewoS9R) was investigated in the new high-throughput micronucleus assay. In total, 12 different mutagenic or genotoxic chemicals were investigated to assess the potential use of the animal-free metabolization system (ewoS9R) in comparison to a common rat-derived product. Out of the 12 compounds, one compound did not induce micronuclei in any treatment and 2 substances showed a genotoxic potential without the need for a metabolization system. EwoS9R demonstrated promising potential for future applications as it shows comparable results to the rat-derived S9 for 6 of the 9 pro-genotoxic substances tested. The remaining 3 substances (2-Acetamidofluorene, Benzo[a]pyrene, Cyclophosphamide) were only metabolized by rat-derived S9. A potential explanation is that ewoS9R was investigated with an approx. 10-fold lower enzyme concentration and was only optimized for CYP1A metabolization that may be improved with a modified production procedure. Future applications of ewoS9R go beyond the micronucleus assay, but further research is necessary.


Asunto(s)
Benzo(a)pireno , Mutágenos , Animales , Línea Celular , Cricetinae , Ciclofosfamida , Pruebas de Micronúcleos , Mutágenos/toxicidad , Ratas
2.
Sci Total Environ ; 750: 141404, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33182165

RESUMEN

The toxic effect of high-dose of short-chain chlorinated paraffins (SCCPs) has been extensively studied, however the possible health risks induced by SCCPs at low-dose remain largely unknown. In this study, a comprehensive toxicology analysis of SCCPs was conducted with the exposure levels from the environmental dose to the Lowest Observed Adverse Effect Level (LOAEL) of 100 mg/kg/day. General toxicology analysis revealed inconspicuous toxicity of the environmental dose of SCCPs, high dose SCCP exposure inhibited the growth rate and increased the liver weight of rat. Metabolomics analysis indicated that SCCP-induced toxicity was triggered at environmentally relevant doses. First, inhibition of energy metabolism was observed with the decrease in blood glucose and the dysfunction of TCA cycle, which may have contributed to lower body weight gain in rats exposed to a high dose of SCCPs. Second, the increase of free fatty acids indicated the acceleration of lipid metabolism to compensate for the energy deficiency caused by hypoglycemia. Lipid oxidative metabolism inevitably leads to oxidative stress and stimulates the up-regulation of antioxidant metabolites such as GSH and GSSH. The up-regulation of polyunsaturated fatty acids (PUFAs) and phospholipids composed of arachidonic acid indicates the occurrence of inflammation. Dysfunction of lipid metabolism can be an indicator of SCCP-induced liver injury.


Asunto(s)
Hidrocarburos Clorados , Parafina , Animales , China , Monitoreo del Ambiente , Hidrocarburos Clorados/análisis , Hidrocarburos Clorados/toxicidad , Metabolismo de los Lípidos , Masculino , Metabolómica , Parafina/análisis , Parafina/toxicidad , Ratas , Ratas Sprague-Dawley
3.
Sci Total Environ ; 750: 141685, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32862004

RESUMEN

Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine ß synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats.


Asunto(s)
Cistationina gamma-Liasa , Metformina , Animales , Compuestos de Bencidrilo/toxicidad , Cromatografía Liquida , Cistationina betasintasa/metabolismo , Cistationina gamma-Liasa/metabolismo , Humanos , Hígado/metabolismo , Masculino , Metformina/toxicidad , Fenoles , Ratas , Espectrometría de Masas en Tándem , Regulación hacia Arriba
4.
Sci Total Environ ; 751: 141734, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32882555

RESUMEN

We estimated associations between ambient air pollution, home environment and asthma as well as rhinitis among adults across China. A total of 40,279 young adults from eight Chinese cities participated in a questionnaire survey (participation rate 75%). There were questions on health and home environment. Information on city level gross domestic product (GDP) per capita, ambient temperature and PM10 and NO2 were collected from registers. Two-level logistic regression models were used to study health associations. Totally 1.6% reported asthma and 6.6% reported allergic rhinitis (AR). Higher temperature was associated with more asthma but less AR. Higher GDP was associated with less asthma but more AR. Higher degree of urbanization, higher level of NO2 and living near heavily trafficked road were risk factors for asthma and AR. Participants in older buildings reported more asthma. Redecoration and buying new furniture were related to more asthma and AR (OR = 1.15-1.91). Using natural gas (OR = 1.34) and biomass (OR = 1.35) for cooking were risk factors for AR. Burning mosquito coils and incense increased the risk of asthma and AR. Cat keeping (OR = 2.88), dog keeping (OR = 2.04), cockroaches (OR = 1.54) and rats or mice (OR = 1.46) were associated with asthma. Cockroaches increased the risk of AR (OR = 1.22). Air humidifier and air cleaner were linked to asthma and AR. Frequent cleaning and exposing bedding to sunshine were protective. In conclusion, urbanization, NO2 and traffic exhaust can increase the risk of adult asthma and AR. Higher ambient temperature was related to more asthma but less AR. Indoor animals such as cats, dogs, rats/mice and presence of cockroaches were associated with asthma or AR. Indoor chemical sources such as redecoration and new furniture were other risk factors. Cooking with natural gas or biomass and burning mosquito coils and incense were associated with asthma or AR. Frequent cleaning and exposing bedding to sunshine were protective.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Asma , Rinitis Alérgica , Anciano , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Animales , Asma/epidemiología , Gatos , China/epidemiología , Ciudades , Perros , Humanos , Ratones , Ratas , Rinitis Alérgica/epidemiología , Factores de Riesgo , Adulto Joven
5.
Sci Total Environ ; 753: 141962, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-32890875

RESUMEN

Arsenic (As) is a known human carcinogen with a hitherto unknown mechanism of action. Dimethylarsinic acid (DMAV) is a methylated metabolite of arsenicals found in most mammals, and long-term exposure to DMAV can lead to bladder cancer in rats. Human epidermal growth factor receptor 2 (HER2) is an oncogenic factor that is overexpressed in bladder cancer, but its role in the initiation and progression of As-induced bladder cancer has not been elucidated. We found that HER2 was up-regulated in human uroepithelial cells treated with arsenite as well as in the bladder tissues of DMAV-exposed rats. HER2 overexpression correlated to increased cell proliferation, epithelial-to-mesenchymal transition (EMT), migration and angiogenesis in vitro. The anti-HER2 monoclonal antibody trastuzumab significantly decreased serum vascular endothelial-derived growth factor (VEGF) levels and that of proliferation-related proteins in the bladder tissues of DMAV-exposed rats. Furthermore, inhibition of HER2, as well as that of the MAPK, AKT and STAT3 pathways, attenuated arsenite-induced proliferation, migration and angiogenesis of human uroepithelial cells, and increased apoptosis rates in vitro. These findings indicate that HER2 mediates the oncogenic effects of As on bladder epithelial cells by activating the MAPK, PI3K/AKT and Src/STAT3 signaling pathways, and is therefore a promising biomarker.


Asunto(s)
Arsénico , Animales , Arsénico/toxicidad , Proliferación Celular , Células Epiteliales , Humanos , Fosfatidilinositol 3-Quinasas , Ratas , Receptor ErbB-2 , Transducción de Señal
6.
Chemosphere ; 262: 127792, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32805656

RESUMEN

Tebuconazole is a triazole fungicide, used in agriculture to treat phytopathogenic fungi, and as a biocide, has been reported to be related to reproductive and developmental toxicity. The purpose of this study was to investigate the effect of tebuconazole exposure on rat fetal Leydig cells and fetal testis during pregnancy. Pregnant Sprague-Dawley rats were randomly divided into 4 groups, daily gavaged with corn oil (as a control), 25, 50, and 100 mg/kg body weight tebuconazole for 10 days (from the 12th day of pregnancy). Tebuconazole increased fetal serum testosterone and progesterone levels at a dose of 100 mg/kg. Exposure to 100 mg/kg tebuconazole significantly caused an increase in the number of fetal Leydig cells per testis without inducing cell aggregation. Tebuconazole up-regulated the expression of Star, Cyp11a1, Hsd17b3, and Fshr and their proteins. Further investigation found that tebuconazole caused increased phosphorylation of AKT1, ERK1/2, and mTOR, the level of BCL2, as well as the decrease of Beclin1, LC3B, and BAX, which may contribute to the fetal Leydig cell autophagy and proliferation. In conclusion, in utero exposure of tebuconazole causes the proliferation of fetal Leydig cells.


Asunto(s)
Fungicidas Industriales/toxicidad , Células Intersticiales del Testículo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Reproducción/efectos de los fármacos , Triazoles/toxicidad , Animales , Femenino , Células Intersticiales del Testículo/metabolismo , Masculino , Fosfoproteínas/genética , Fosforilación , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Testículo/efectos de los fármacos , Testículo/embriología , Testículo/patología , Testosterona/sangre , Regulación hacia Arriba
7.
Gene ; 764: 145083, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32860902

RESUMEN

BACKGROUND/AIMS: Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage. METHOD: Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800 mg/kg bw), ML (700 mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined. RESULTS: ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats. CONCLUSION: MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Moringa oleifera/química , Extractos Vegetales/administración & dosificación , Insuficiencia Renal/prevención & control , Triazinas/toxicidad , Administración Oral , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/inmunología , Moléculas de Adhesión Celular/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Modelos Animales de Enfermedad , Contaminantes Ambientales/toxicidad , Etanol/química , Contaminación de Alimentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Estrés Oxidativo/inmunología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Insuficiencia Renal/sangre , Insuficiencia Renal/inducido químicamente , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Triazinas/administración & dosificación
8.
Gene ; 766: 145128, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32911026

RESUMEN

BACKGROUND: The pathogenesis of osteonecrosis of the femoral head (ONFH) is unclear. Our previous study demonstrated that upregulated miR-335 in bone microvascular endothelial cells (BMECs) might be associated with the disease of steroid-induced ONFH. Here, we study the preventive effect of ICA on steroid-induced ONFH in rats. METHOD: 90 rats were separated into three groups: control group, methylprednisolone (MPS) group, and MPS + Icariin (ICA) group. Four weeks later, histological analyses were performed. Thrombomodulin (TM) and vascular endothelial growth factor (VEGF) were tested. MiRNA-335 expression was screened in the three groups using Agilent Gene Spring GX software. Target genes of miRNA-335 were detected by bioinformatics analysis. The functions of BMECs were analyzed by scratch, angiogenesis and cell survival rate. RESULTS: ICA can prevent the occurrence of steroid-associated ONFH in rats and reduce the amount of TM and VEGF in serum induced by glucocorticoids. ICA could regulate the overexpression of miRNA-335 induced by glucocorticoids. We predicted the Gene ontology (GO) and signaling pathways of target genes. At 24 hours, we found that ICA significantly promoted BMECs migration abilities. We also found that ICA could promote the angioplasty ability of BMECs. ICA could improve the survival rate of BMECs after steroid-induced injury. CONCLUSIONS: ICA is effective to prevent the occurrence of steroidinduced ONFH. ICA has a protective effect against steroid-induced BMECs injury. ICA regulated the imbalance of miRNA-335 expression induced by the glucocorticoid in BMECs, which provides a new viewpoint to explore the mechanism of ICA in preventing steroid-induced ONFH.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Cabeza Femoral/efectos de los fármacos , Flavonoides/farmacología , MicroARNs/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Sustancias Protectoras/farmacología , Adipogénesis/efectos de los fármacos , Animales , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Endoteliales/metabolismo , Femenino , Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/metabolismo , Glucocorticoides/metabolismo , Metilprednisolona/farmacología , Neovascularización Patológica/metabolismo , Osteocitos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Esteroides/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo
9.
Gene ; 766: 145154, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32949699

RESUMEN

CircRNA serves a crucial role in the development of heart failure (HF). Nevertheless, the regulatory mechanisms of circ_0062389 in HF are unknown. This study aims to examine the effect and mechanism of circ_0062389 on cardiomyocyte apoptosis in HF rats and H9C2 cells. Rats were divided into 5 groups (n = 8/group): the Control group, Sham group, HF group, HF + si-NC group, and HF + si-circRNA group. The echocardiography was used to examine the cardiac function, including LVIDd, LVIDs, IVSd, and IVSs. The apoptosis of myocardial tissue was detected through TUNEL method. H9C2 cells were randomly assigned into Control group (untransfected H9C2 cells), H/R group (untransfected H/R H9C2 cells), H/R + si-NC group (transfected si-NC) and H/R + si-circRNA group (transfect si-circ_0062389). Cell apoptosis was assessed through flow cytometry. The expression of circ_0062389 in myocardial tissues of HF rats was significantly higher than that of Control group and Sham group. Silencing circ_0062389 significantly reduced the levels of LVIDd, LVIDs, IVSd, and IVSs. Additionally, silencing circ_0062389 could significantly reduce the apoptosis rate of rat cardiomyocytes. Besides, silencing circ_0062389 significantly reduced the expression of TGF-ß1 and Smad3 protein. Silencing circ_0062389 could alleviate cardiomyocyte apoptosis in HF rats via modulating TGF-ß1/Smad3 signaling pathway, which might be a promising target for the treatment of HF.


Asunto(s)
Apoptosis/genética , Insuficiencia Cardíaca/genética , Miocitos Cardíacos/patología , Interferencia de ARN/fisiología , ARN Circular/genética , Transducción de Señal/genética , Proteína smad3/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Línea Celular , Corazón/fisiología , Insuficiencia Cardíaca/patología , Masculino , Miocardio/patología , Ratas , Ratas Sprague-Dawley
10.
Gene ; 766: 145153, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32950633

RESUMEN

AIM: Acute lung injury (ALI) is the mild form of acute respiratory distress syndrome (ARDS) which is a common lung disease with a high incidence and mortality rate. Recent studies manifested that some circular RNAs were associated with ALI. In this study, we aimed to uncover the effect of circular RNA circ_0054633 on ALI initiation and progression and proposed a new mechanism related to ALI. METHODS: The lipopolysaccharides (LPS)-induced acute lung injury model were build both in vivo of rat and in vitro of primary murine pulmonary microvascular endothelial cells (MPVECs). Hematoxylin and eosin (H&E) was employed to observe the tissue morphology and estimate the degree of lung damage. We used real-time quantitative polymerase chain reaction (RT-qPCR) to measure the expression level of circ_0054633. The expression levels of inflammatory cytokines IL-17A and tumor necrosis factor-α (TNF-α) were detected by ELISA. The effects of circ_0054633 on MPVECs proliferation and apoptosis were detected with the help of CCK-8 and apoptosis assay, separately. The expression level of NF-κB p65 protein was measured by Western blot. RESULTS: circ_0054633, IL-17A, TNF-α and NF-κB p65 were all overexpressed in LPS-treated rat and MPVECs, and LPS enhanced the proliferation and apoptosis of MPVECs. While circ_0054633 silencing reversed the above promotion effects of LPS on IL-17A, TNF-α expression and MPVECs proliferation and apoptosis. CONCLUSIONS: Quietness of circ_0054633 alleviated LPS-induced ALI via NF-κB signaling pathway, implicating circ_0054633 may be a potential biomarker for diagnose and therapy of ALI.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Proliferación Celular/fisiología , Células Endoteliales/metabolismo , Inflamación/metabolismo , FN-kappa B/metabolismo , ARN Circular/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Inflamación/inducido químicamente , Interleucina-17/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
11.
Gene ; 766: 145155, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32950634

RESUMEN

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.


Asunto(s)
Adipocitos Marrones/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Epidídimo/efectos de los fármacos , Nitratos/administración & dosificación , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Epidídimo/metabolismo , Glucosa/metabolismo , Insulina/sangre , Masculino , PPAR gamma/genética , PPAR gamma/metabolismo , ARN Mensajero/genética , Ratas , Ratas Wistar , Estreptozocina/farmacología
12.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(11): 1405-1409, 2020 Nov 15.
Artículo en Chino | MEDLINE | ID: mdl-33191698

RESUMEN

Objective: To observe the expressions of transforming growth factor ß 1 (TGF-ß 1) and basic fibroblast growth factor (bFGF) induced membrane by Masquelet technique in rats treated with glycoside of short-horned epimedium Herb, and to explore the effect of glycoside of short-horned epimedium Herb on Masquelet induced membrane. Methods: Sixty 3-month-old male Wistar rats were randomly divided into 3 groups with 20 rats in each group; a tibial bone defect (6 mm in length) model was established. The blank group (group A) was not treated; the control group (group B) and the experimental group (group C) were filled with vancomycin antibiotic bone cement in the drawing stage, and the bone cement was completely solidified. Group C was given perfused flavonoids glycoside of short-horned epimedium Herb (10 µmol/L) by gavage once a day (0.3 mL) from 1 day after operation, and groups A and B were given the same amount of normal saline by gavage. After operation, the recovery and wound healing of experimental animals were observed; at 4 weeks after operation, X-ray film was taken to observe the recovery of bone defect of proximal tibia; at 6 weeks after operation, the bone defect was observed, and the morphological changes and vascularization degree of granulation tissue and induction membrane tissue were observed; the expressions of TGF-ß 1 and bFGF were observed by immunohistochemistry staining and ELISA detection. Results: The bone defect models of the 3 groups were established successfully, and there was no abnormality after operation. The incisions healed by first intention after operation. At 4 weeks after operation, X-ray films of proximal tibial defect showed that there was obvious space in group A, while bone cement was filled and Kirschner wire fixation was good in groups B and C. At 6 weeks after operation, the gross observation showed that the granulation tissue was filled in the defect area in group A; transparent membrane was formed in groups B and C, and microvessels were seen in some areas, and the microvessels in group C were significantly more than those in group B. Immunohistochemical staining showed that the expressions of TGF-ß 1 and bFGF were negative in group A, but they were expressed in groups B and C, and the expressions of TGF-ß 1 and bFGF in group B were significantly less than those in group C. ELISA detection showed that the expressions of TGF-ß 1 and bFGF in group C were significantly higher than those in groups A and B ( P<0.05), but there was no significant difference between groups A and B ( P>0.05). Conclusion: Glycoside of short-horned epimedium Herb can significantly increase the expressions of TGF-ß 1 and bFGF, accelerate the process of osteogenesis, and contribute to bone shaping and reconstruction.


Asunto(s)
Epimedium , Factor 2 de Crecimiento de Fibroblastos , Animales , Glicósidos/farmacología , Masculino , Ratas , Ratas Wistar , Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta1 , Cicatrización de Heridas
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(11): 1429-1437, 2020 Nov 15.
Artículo en Chino | MEDLINE | ID: mdl-33191702

RESUMEN

Objective: To study the local vascular remodeling, inflammatory response, and their correlations following acute spinal cord injury (SCI) with different grades, and to assess the histological changes in SCI rats. Methods: One hundred and sixteen adult female Sprague Dawley rats were randomly divided into 4 groups ( n=29). The rats in sham group were received laminectomy only. A standard MASCIS spinal cord compactor was applied with drop height of 12.5, 25.0, or 50.0 mm to establish the mild, moderate, or severe SCI model, respectively. Quantitative rat endothelial cell antigen 1 (RECA1) and CD68 positive areas and the correlations were studied by double immunofluorescent (DIF) staining at 12 hours, 24 hours, 3 days, 7 days, and 28 days following SCI. Moreover, qualitative neurofilament-H (NF-H) and glial fibrillary acidic protein (GFAP) positive glial cells were studied by DIF staining at 28 days. ELISA was used to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in spinal cord homogenates at 12 hours, 24 hours, and 3 days, and the correlations between TNF-α, IL-1ß, or IL-6 levels and microvascular density (RECA1) were accordingly studied. Moreover, the neural tissue integrity and neuron damage were assessed by HE staining at 12 hours, 24 hours, 3 days, 7 days, and 28 days, and Nissl's staining at 28 days following SCI, respectively. Results: DIF staining revealed that the ratio of RECA1 positive area was the highest in moderate group, higher in mild and severe groups, and the lowest in sham group with significant differences between groups ( P<0.05). The ratio of CD68 positive area was the highest in severe group, higher in moderate and mild groups, and the lowest in sham group with significant differences between groups ( P<0.05), except the comparisons between mild and moderate groups at 24 hours and 28 days after SCI ( P>0.05). There was no significant correlation between the RECA1 and CD68 expressions in sham group at different time points ( P>0.05). At 12 and 24 hours after SCI, the RECA1 and CD68 expressions in mild and moderate groups showed significant positive correlations ( P<0.05), while no significant correlation was found in severe group ( P>0.05). No significant correlations between the RECA1 and CD68 expressions was shown in all SCI groups at 3 days and in severe group at 7 days ( P>0.05), while the negative correlations were shown in mild and moderate groups at 7 days, and in all SCI groups at 28 days ( P<0.05). In mild, moderate, and severe groups, the axons became disrupted, shorter and thicker rods-like, or even merged blocks with increased injury, while the astrocytes decreased in number, unorganized and condensed in appearance. ELISA studies showed that TNF-α, IL-1ß, and IL-6 levels in sham group were significantly lower than those in other 3 groups at different time points ( P>0.05). The differences in TNF-α, IL-1ß, and IL-6 levels between SCI groups at different time points were sinificant ( P<0.05), except IL-1ß levels between the mild and moderate groups at 12 hours ( P>0.05). Three inflammatory factors were all significantly correlated with the microvascular density grades ( P<0.05). Histological analysis indicated that the damage to spinal cord tissue structure correlated with the extent of SCI. In severe group, local hemorrhage, edema, and infiltration of inflammatory cells were found the most drastic, the grey/white matter boundary was disappeared concurrently with the formation of cavity and shortage of normal neurons. Conclusion: In the acute stage following mild or moderate SCI, progressively aggravated injury result in higher microvessel density and increased inflammation. However, at the SCI region, the relation between microvessel density and inflammation inverse with time in the different grades of SCI. Accordingly, the destruction of neural structures positively relate to the grades of SCI and severity of inflammation.


Asunto(s)
Traumatismos de la Médula Espinal , Remodelación Vascular , Animales , Femenino , Ratas , Ratas Sprague-Dawley , Médula Espinal , Factor de Necrosis Tumoral alfa
14.
An Acad Bras Cienc ; 92(4): e20191026, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206784

RESUMEN

Chlorothalonil and thiophanate-methyl are fungicides widely used in agriculture. The aim of this study was to assess maternal toxicity and embryotoxic potential of exposure to chlorothalonil and thiophanate-methyl during organogenesis period in rats. Pregnant rats were divided into four groups: control and exposed to 400 (CT400), 800 (CT800) and 1200 mg-1kg bw-1 day (CT1200) of commercial formulation constituted of 200 g of thiophanate-methyl kg-1 and 500 g of chlorothalonil kg-1 by gavage, from 6th to 15th gestational day. Maternal toxicity, liver, kidney and placenta histology, reproductive performance, and external, skeletal and visceral malformations of fetuses were evaluated. Maternal liver weight was decreased in CT1200 group and focal necrosis and microvesicular steatosis, inflammatory infiltrate and hepatocytes with pyknotic nucleus were observed in CT800 and CT1200 groups. Reproductive performance was similar among groups. The percentage of fetuses small for pregnancy age was increase in CT400 and CT800 groups. Moreover, incidence of skeletal anomalies was increased in the three groups exposed to fungicides. Chlorothalonil and thiophanate-methyl exposure showed affect the prenatal development and induce maternal toxicity.


Asunto(s)
Organogénesis , Tiofanato , Animales , Femenino , Feto , Nitrilos/toxicidad , Embarazo , Ratas
15.
An Acad Bras Cienc ; 92(4): e20191584, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206788

RESUMEN

In this work, the natural latex extracted from Harconia speciosa was incorporated with silver nanoparticles (AgNP) to compose a functional biomaterial associating the intrinsic angiogenic activity of the latex and the antimicrobial activity of AgNP. Tissue reaction after subcutaneous implantation in dorsum of rats of membranes without AgNP and with 0.05%, 0.4% AgNP was compared at 3, 7 and 25 days. No statistically significant difference in the tissue response of the different biomaterials was observed, indicating that AgNP did not interfere with the inflammatory reaction (p > 0.05) or with the angiogenic activity of latex. Biomembranes were also tested against bacterial biofilm formation by Staphylococcus aureus and the antimicrobial activity of the new biomaterial can be found with bacteria crenation (0.05% AgNP) and no biofilm deposition (0.4% AgNP). Therefore, this biomaterial has interesting properties for the tissue repair process and may be feasible for future applications as dressing.


Asunto(s)
Látex , Nanopartículas del Metal , Animales , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Biopelículas , Ratas , Plata/farmacología
16.
An Acad Bras Cienc ; 92(4): e20200012, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206789

RESUMEN

Professional athletes conduct high-intensitive hypoxic training often accompanied by the increase of many inflammatory-related cytokines and immunosuppression. Cucurbitacin E (CucE), as a triterpenoid isolated from Cucurbitaceae plants, exert potential anti-cancer and anti-inflammatory. However, it is unknown whether that the CucE could be used as dietary supplement for athletes to improve inflammatory response and immunosuppression. In this study, we established the simulative hypoxic training rat and monkey models and evaluated the effects of CucE on immune- and inflammation-related factors. Obvious improvement on pro-inflammatory factors and pro-lymphocyte proliferation activities were showed in CucE treated rats compared with the control. Further supplement of CucE in professional meals for cynomolgus monkeys with 4-weeks high-intensitive hypoxic training also exert effects on altitude-induced oxidative stress, inflammation and immunologic function. Furtherly, we explored the underlying mechanism of CucE in human Jurkat T cells and results showed that CucE may exhibit immunosuppressive effect by attenuating critical cytokine expression through down-regulating the NF-κB signaling pathway. In conclusion, CucE is expected to be a potential dietary supplement for athletes to ameliorate the inflammation and immunosuppression caused by high-intensitive exercise.


Asunto(s)
Altitud , Triterpenos , Animales , Citocinas/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Ratas , Triterpenos/farmacología
17.
An Acad Bras Cienc ; 92(4): e20200067, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206790

RESUMEN

Urolithiasis is a disorder of kidneys in which stones formation occur due to the excessive deposition of minerals in the urinary tract. It affects 12% of the population worldwide. Salvia hispanica seeds are rich source of quercetin which has preventive role in renal stone formation. The study objective was to explore scientifically the anti-urolithiatic effect of Salvia hispanica seed's methanol extract using in vitro and in vivo urolithiasis models. For in-vitro study nucleation, growth and aggregation assays were performed. In vivo study was performed on rats and they were divided into six groups (n=6). Group-I was given vehicle only. Group-II was disease control, treated with 0.75% EG in drinking water which triggered urolithiasis. Groups-III received cystone (750 mg/kg, orally). Groups IV-VI were treated with extract at 100, 300 and 700 mg/kg doses orally once daily. Groups III-VI additionally received 0.75% EG in drinking water. In vitro study revealed concentration dependent increase in percentage inhibition of crystal's nucleation, growth and aggregation. In vivo study revealed anti-urolithiatic activity by lowering oxalate, calcium, phosphate, sodium and potassium levels in the urine and the serum uric acid, blood urea nitrogen, total proteins and total albumin. Salvia hispanica seeds are good alterative of allopathic anti-urolithiatic drugs to treat urolithiasis.


Asunto(s)
Salvia , Urolitiasis , Animales , Glicol de Etileno , Extractos Vegetales/farmacología , Ratas , Semillas , Ácido Úrico , Urolitiasis/inducido químicamente , Urolitiasis/tratamiento farmacológico
18.
Urologiia ; (5): 99-105, 2020 Nov.
Artículo en Ruso | MEDLINE | ID: mdl-33185356

RESUMEN

The current trends in understanding the pathogenesis of infectious and inflammatory urogenital disorders are highlighted in the review. The etiological and pathogenetic significance of increased intestinal permeability for pathogens in the development of various diseases has been convincedly proved. There is no doubt about the pathogenetic role of increased permeability of the bladder mucosa, which can result in interstitial cystitis (IC). The association of intestinal diseases with IC has been established. In rats, the induction of intestinal inflammation may cause increased permeability of the bladder mucosa. In the postoperative period, bacteria are translocated from the gastrointestinal tract to the urinary tract, which is associated with stress. Particular attention is paid to the therapy based on new knowledge about the pathogenesis of infectious and inflammatory diseases of the urogenital tract. Possibilities of decreasing intestinal and bladder permeability using rebamipide are described. Various therapeutic mechanisms of action made it possible to use this drug in endoscopy, ophthalmology, chemotherapy and rheumatology. The antioxidant and anti-inflammatory properties of rebamipide has been shown in-vitro. Intravesical instillation of rebamipide accelerates the recovery of damaged urothelium and its barrier function, and also influences on bladder hyperactivity. Thus, the first results of using rebamipide in urology are encouraging; however, further researches are required.


Asunto(s)
Cistitis Intersticial , Administración Intravesical , Animales , Cistitis Intersticial/tratamiento farmacológico , Cistitis Intersticial/etiología , Inflamación/tratamiento farmacológico , Ratas , Urotelio
19.
J Biomed Nanotechnol ; 16(6): 899-909, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33187585

RESUMEN

A well-studied subject of epigenetics, the histone methylation located at lysine and arginine is overseen via methyltransferases and demethylases. Lysine-specific demethylase 4A (KDM4A) comprises a lysine demethylase and possesses specificity for H3K9me3 and H3K36me3, which is capable of being used in order to activate histone transcription. Our team examined the expression of KDM4A within Sprague Dawley (SD) rats and further investigated the mechanism via which this phenomena regulates osteogenic variation within the present study. The overexpression of KDM4A facilitated the process of osteoblast differentiation in bone mesenchymal stem cells (BMSC), while the knocking down differentiation via osteoblast was restrained via the suppression of the expression of Runx2, Osterix, alkaline phosphatase (ALP), and osteocalcin (OCN). Knocking down KDM4A lowered levels of the promoter expression of Runx2, osterix, and OCN, and raised levels of H3K27me3 expression. The results demonstrated that KDM4A possesses a crucial role within the differentiation of osteoblasts and furthermore regulates the expression of Runx2, Osterix, and OCN via H3K9me3. The present research may provide new insights into the treatment of bone healing.


Asunto(s)
Histona Demetilasas , Lisina , Osteogénesis , Animales , Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Histona Demetilasas/fisiología , Osteoblastos/metabolismo , Osteocalcina/genética , Osteogénesis/genética , Ratas , Ratas Sprague-Dawley , Receptores de Oxitocina , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
20.
Zhonghua Xin Xue Guan Bing Za Zhi ; 48(11): 962-967, 2020 Nov 24.
Artículo en Chino | MEDLINE | ID: mdl-33210869

RESUMEN

Objective: To observe the impact and difference of resection of left stellate ganglion (LSG) or right stellate ganglion (RSG) on rats with heart failure. Methods: Thirty male SD rats were divided into 3 groups (n=10 each) by random number table method: control group, LSG group, RSG group. All three groups underwent TAC surgery to establish a pressure-overloaded heart failure model. Then, LSG and RSG were bluntly separated and removed in rats assigned to the LSG group or RSG group by surgery, while rats in the control group underwent sham operation. The changes in blood pressure and heart rate before operation, 30 minutes and 10 weeks after operation were recorded; echocardiography was performed before operation and 10 weeks after operation to detect the thickness of the ventricular septum, left ventricle posterior wall diameter, left ventricular end diastolic diameter, left ventricular end diastolic volume, and calculate the left ventricular fractional shortening and left ventricular ejection fraction. HE staining and Masson staining were performed to observe the degree of myocardial hypertrophy and myocardial fibrosis, and to judge the ventricular remodeling. Results: The heart rates of the three groups of rats were (352.4±4.3), (320.3±4.0) and (297.9±5.9) beats/min, and the blood pressure was (142.8±2.3), (123.4±2.7) and (129.6±2.9) mmHg(1 mmHg=0.133 kPa) at thirty minutes after surgery; the heart rates of the three groups of rats were (352.9±4.0), (321.6±3.4) and (301±4.1) beats/min, and the blood pressure was (145.6±1.9), (124.8±1.7) and (130.4±4.4) mmHg at 10 weeks after surgery. The heart rate and blood pressure in the LSG group and RSG group at 30 min and 10 weeks after surgery were significantly lower than those in the control group; at 10 weeks after surgery, the heart rate in the RSG group was significantly lower than that in the LSG group (P both<0.001). After 10 weeks, rats in the control group developed severe left ventricular dilatation. Degree of left ventricular hypertrophy was significantly reduced in the LSG group and RSG group than in the control group, the thickness of the ventricular septum was (3.2±0.3), (2.5±0.1) and (2.5±0.1) mm; the left ventricular end-diastolic diameters were (7.5±0.3), (5.5±0.3) and (5.7±0.2) mm; the left ventricular end-diastolic volume was (9.5±0.3), (4.5±0.2) and (4.8±0.2) ml; the left ventricular fractional shortening was (21.6±1.3)%, (49.1±3.9)% and (47.4±1.5)%; and the left ventricular ejection fraction was (50.9±2.5)%, (81.9±2.1)% and (80.0±2.3)%, respectively in the control group, LSG group and RSG group. Compared with the control group, the left ventricular posterior wall diameter, left ventricular end-diastolic diameter and left ventricular end-diastolic volume were significantly lower and the left ventricular fractional shortening and left ventricular ejection fraction were significantly higher in the LSG group and RSG group (all P<0.001). 10 weeks after operation, the values of type Ⅰ collagen in the control group, LSG group, and RSG group were (0.354±0.013), (0.211±0.012) and (0.243±0.013), respectively. Ratio of type Ⅰ/Ⅲ collagen was (1.109±0.065), (0.737±0.055) and (0.839±0.075), respectively. Compared with the control group, the ratio of type Ⅰcollagen and ratio of type Ⅰ/Ⅲ collagen were significantly lower in the LSG group and RSG group (P<0.001). Conclusion: Both left and right stellate ganglion resection can similarly reduce ventricular remodeling caused by pressure overload and delay the progression of heart failure in tis TAC rat model.


Asunto(s)
Insuficiencia Cardíaca , Función Ventricular Izquierda , Animales , Insuficiencia Cardíaca/cirugía , Ventrículos Cardíacos , Masculino , Ratas , Ratas Sprague-Dawley , Volumen Sistólico
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