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1.
J Enzyme Inhib Med Chem ; 35(1): 31-41, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31645149

RESUMO

The present study describes the synthesis of a novel series of thiazolidin-4-one and thiazinan-4-one using 1-(2-aminoethyl)pyrrolidine as amine precursor. All compounds were synthesised by one-pot three component cyclocondensation reaction from the amine, a substituted benzaldehyde and a mercaptocarboxylic acid. The compounds were obtained in moderate to good yields and were identified and characterised by 1H, 13 C, 2 D NMR and GC/MS techniques. The compounds also were screened for their in vitro acetylcholinesterase (AChE) activity in hippocampus and cerebral cortex on Wistar rats. The six most potent compounds have been investigated for their cytotoxicity by cell viability assay of astrocyte primary culture, an important cell of central nervous system. We highlighted two compounds (6a and 6k) that had the lowest IC50 in hippocampus (5.20 and 4.46 µM) and cerebral cortex (7.40 and 6.83 µM). These preliminary and important results could be considered a starting point for the development of new AChE inhibitory agents.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Tiazinas/farmacologia , Tiazolidinas/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Estrutura Molecular , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazinas/síntese química , Tiazinas/química , Tiazolidinas/síntese química , Tiazolidinas/química
2.
Arch Oral Biol ; 109: 104553, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31563004

RESUMO

This study evaluated the effects of replacing a saturated fat diet by n-3 polyunsaturated fatty acids (n-3PUFA), on alveolar bone loss in hypercholesterolemic rats with experimental periodontitis (PD). METHODS: Eight week old Wistar rats were assigned according to dietary intake. Control group (C, n = 15) fed a commercial diet throughout the experiment. Atherogenic group (AT, n = 30) fed AT diet for 3 weeks; thereafter, AT was randomized to receive either a n-3PUFA (n = 15) or to continue with AT (n = 15) diet. Subsequently, PD was induced in all groups by unilateral ligature (L) of the first molar (M1) of the left mandible, non-ligated contralateral molars served as controls. After every week of PD induction, 5 rats per group were euthanized. Serum was collected for lipids assays and hemi-mandibles were subjected to histomorphometric (% upper and lower interradicular bone volume and periodontal ligament height, hPDL) and radiographic analyses (periodontal bone support, PBS, in ligated teeth, between M1-M2). RESULTS: Rats fed n-3PUFA diet rapidly induced a significant reduction in the serum lipids (p < 0.001). In all rats the ligated teeth showed a greater bone loss as compared with the unligated molars. At the end of the experiment the AT + L was the worst in % lower bone volume (p < 0.01), hPDL and PBS (p < 0.05). In contrast, rats fed n-3PUFA + L was similar to those rats fed C diet (p > 0.05). CONCLUSION: Alveolar bone and dyslipidemia improved by substituting saturated fat intake for a n-3PUFA rich diet, in hypercholesterolemic rats with PD.


Assuntos
Perda do Osso Alveolar/terapia , Dieta , Ácidos Graxos Ômega-3/administração & dosagem , Óleos de Peixe/administração & dosagem , Hipercolesterolemia/fisiopatologia , Periodontite/fisiopatologia , Animais , Dislipidemias/terapia , Distribuição Aleatória , Ratos , Ratos Wistar
3.
J Sci Food Agric ; 100(2): 705-713, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31599967

RESUMO

BACKGROUND: Despite the growing importance of probiotics apparent health benefits, an impediment to the use of new probiotic cultures is their safety. Hence there is a need to strictly examine the biosafety as well as health benefits of probiotics in in vivo model systems. RESULTS: In this study, two lactic acid bacterial (LAB) cultures Lactobacillus fermentum NCMR 2826 and FIX proven for their in vitro probiotic properties were investigated for their in vivo safety in Wistar rats. An acute toxicity study (14 days) with a high dose of biomass (1016 colony-forming units (CFU) mL-1 ) followed by a subchronic test for 13 weeks with oral feeding of the probiotic cultures in three different doses (107 , 108 and 1010 CFU mL-1 ) on a daily basis revealed the safety of the L. fermentum cultures. The probiotic feeding had no toxic effects on survival, body weight and food consumption with any of the dosages used throughout the treatment period. No statistically significant changes in relative organ weights and serum biochemical and hematological indices were found between the control and the probiotic fed animals. In addition to the safety attributes, the L. fermentum culture fed rats showed reduced serum cholesterol levels, macrovesicular steatosis and hepatocyte ballooning compared with control animals. Further, quantification of intestinal microbiota using real-time polymerase chain reaction (PCR) analysis from animal feces indicated a significant increase and stability of Lactobacillus and Bifidobacterium counts but a decrease of Escherichia coli numbers. CONCLUSION: This study of safety and beneficial features highlights the use of the two native L. fermentum isolates as potential probiotic food supplements. © 2019 Society of Chemical Industry.


Assuntos
Anticolesterolemiantes/administração & dosagem , Colesterol/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus fermentum/metabolismo , Probióticos/administração & dosagem , Animais , Anticolesterolemiantes/metabolismo , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colesterol/sangue , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Lactobacillus fermentum/crescimento & desenvolvimento , Masculino , Probióticos/metabolismo , Ratos , Ratos Wistar
4.
Life Sci ; 241: 117154, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31857087

RESUMO

AIM: Insulin resistance and neuroinflammation play roles in Alzheimer's (AD) etiology. Insulin receptors (IR) are developmentally expressed in neurons as well as astrocytes. Moreover, prolonged stress can induce brain insulin resistance and astrogliosis. Also, prenatal stress could advance AD-related abnormalities in a transgenic model of AD. Besides, postnatal maternal care (PMC) has antagonistic effects on prenatal stress (PS)-induced neuronal and immunological malfunctions. Using an icv-STZ subclinical model of sAD, we assessed PS and/or abnormal PMC impacts on advancing sAD-like pathology in adult male rats. We also sought astrocyte- and/or neuron-oriented change in central insulin programming. MAIN METHODS: Pregnant rats were exposed to PS. Thereafter, a group of pups was fostered onto unstressed mothers and the others remained intact. Real-time RT-PCR- for hippocampal IR, Tau, and ChAT transcripts- and immunohistochemistry analysis- for GFAP+ astrocytes- were performed at the first- and forth-postnatal-week, respectively. The other animals received icv-STZ0.5 mg/kg in adulthood and subjected to cognitive tests, molecular, and histological experiments at appropriate time-point post-injection. KEY FINDINGS: PS could advance sAD-related symptoms in icv-STZ-treated animals. PS changed expression levels of hippocampal IR in one-week-old and 5.5-month-old offspring. PS could worsen cognitive, molecular and histological impairments of icv-STZ. Adequate PMC prevented some destructive effects of PS. SIGNIFICANCE: PS can potentially change central insulin programming and induce long-lasting astrogliosis in rat hippocampus. PS-related cognitive and histological pathologies can rescue by PMC probably via IR-dependent pathways. Astrocyte involvement in AD-like neuropathology observed in stressed-animals needs more detailed investigations.


Assuntos
Doença de Alzheimer/patologia , Comportamento Animal , Modelos Animais de Doenças , Resistência à Insulina , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estreptozocina/toxicidade , Estresse Psicológico/complicações , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Animais Recém-Nascidos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Infusões Intraventriculares , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Gravidez , Ratos , Ratos Wistar , Receptor de Insulina/metabolismo , Transdução de Sinais , Estreptozocina/administração & dosagem
5.
Toxicol Lett ; 318: 57-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31585160

RESUMO

3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.


Assuntos
Antineoplásicos/toxicidade , Ventrículos do Coração/efeitos dos fármacos , Inseticidas/toxicidade , Piruvatos/toxicidade , Rotenona/toxicidade , Taquicardia Ventricular/induzido quimicamente , Fibrilação Ventricular/induzido quimicamente , Remodelação Ventricular/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Conexina 43/genética , Conexina 43/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/ultraestrutura , Masculino , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Ratos Wistar , Período Refratário Eletrofisiológico/efeitos dos fármacos , Medição de Risco , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/patologia , Fibrilação Ventricular/fisiopatologia
6.
Ultrasonics ; 101: 106001, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31505328

RESUMO

Ultrasound is the first-line tool for screening hepatic steatosis. Statistical distributions can be used to model the backscattered signals for liver characterization. The Nakagami distribution is the most frequently adopted model; however, the homodyned K (HK) distribution has received attention due to its link to physical meaning and improved parameter estimation through X- and U-statistics (termed "XU"). To assess hepatic steatosis, we proposed HK parametric imaging based on the α parameter (a measure of the number of scatterers per resolution cell) calculated using the XU estimator. Using a commercial system equipped with a 7-MHz linear array transducer, phantom experiments were performed to suggest an appropriate window size for α imaging using the sliding window technique, which was further applied to measuring the livers of rats (n = 66) with hepatic steatosis induced by feeding the rats a methionine- and choline-deficient diet. The relationships between the α parameter, the stage of hepatic steatosis, and histological features were verified by the correlation coefficient r, one-way analysis of variance, and regression analysis. The phantom results showed that the window side length corresponding to five times the pulse length supported a reliable α imaging. The α parameter showed a promising performance for grading hepatic steatosis (p < 0.05; r2 = 0.68). Compared with conventional Nakagami imaging, α parametric imaging provided significant information associated with fat droplet size (p < 0.05; r2 = 0.53), enabling further analysis and evaluation of severe hepatic steatosis.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Modelos Animais de Doenças , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Imagens de Fantasmas , Ratos , Ratos Wistar
7.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4519-4528, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872641

RESUMO

This study was aimed to investigate the mechanism of Danzhi Jiangtang Capsules( DJC) in the treatment of diabetic macrovascular disease in Goto-Kakizaki( GK) rats. The diabetic macrovascular disease rat model was induced by feeding high-fat and high-sugar combined with endothelial nitric oxide synthase( NOS) inhibitor N-nitro-L-arginine methyl ester( L-NAME)( 0. 1 g·L-1·d-1). According to the random array table,the model rats were randomly divided into the model group,DJC groups( 1 260,630,320 mg·kg-1),atorvastatin group( 105 mg·kg-1) and metformin group( 10 mg·kg-1),with 12 rats in each group. The rats received gavage administration for 8 weeks. Twelve Wistar rats were selected as the normal control group. The changes of body weight,water intake,blood glucose,plasma total cholesterol( TC),triglyceride( TG),high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),interleukin( IL-1ß),IL-6,tumor necrosis factor( TNF-α),nitric oxide( NO),endothelin( ET-1) were observed in these rats. Aortic tissue was taken and the pathological changes were observed by HE staining. RT-PCR was used to detect the mRNA levels of IL-1ß,IL-6,and TNF-α in rat aorta. RT-PCR of the stem loop was used to detect the levels of miRNA-126,miRNA-155,miRNA-146 a,and miRNA-21 in rat plasma and aortic tissue. The canonical correlation between miRNAs and inflammatory factors was then analyzed. The results showed that DJC increased the rat body weight,lowered water intake,reduced the random blood glucose,reversed the rat aorta tissue damage,reduced serum TC,TG,LDL-C,ET-1,IL-1ß,IL-6,TNF-α,as well as miRNA-155,miRNA-146 a and miRNA-21 levels in serum,elevated plasma HDL-C,NO content,reduced the aorta mRNA of IL-1ß,IL-6,TNF-α,and the miRNA-155,miRNA-146 a and miRNA-21,elevated miRNA-126 expression in aorta. Aortic miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 expression levels were typically correlated with the expression of inflammatory factors,among which miRNA-126 was negatively correlated,miRNA-155,miRNA-146 a and miRNA-21 were positively correlated with the factors. These results suggested that DJC had therapeutic effects on diabetic macrovascular diseases,and the mechanism of action may be related to the regulation of miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 levels,as well as the reduction of inflammatory factors and vascular inflammatory response.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas/farmacologia , MicroRNAs , Animais , Cápsulas , Medicamentos de Ervas Chinesas/uso terapêutico , Ratos , Ratos Wistar
8.
Int. arch. otorhinolaryngol. (Impr.) ; 23(4): 427-432, Out.-Dez. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024399

RESUMO

Introduction: The bone-implant interface has been studied extensively, but only few papers focused on the nutritional aspects that may affect bone quality, especially salt intake. Objective: To study the osseointegration of implants in salt-loaded rats with low mineral bone content. Methods: A total of 60 4-month-old male rats were divided in 2 groups ( n = 30), being these groups divided in 2 periods, (2 and 4 months). The control group received a normal diet, while the test group received a diet supplemented with 1% sodium chloride (NaCl). Implants were placed in the tibia of both groups. A total of 15 animals of each group were sacrificed at the 2 nd month of the experiment, while the remaining animals were sacrificed at the 4 th month. Results: No statistically significant difference was found in food intake between the groups on any experimental period, but a statistically significant difference was found in the liquid intake in the saline group in both periods. For all groups, osseointegration was observed in both groups. The mean percentage of osseointegration in the cortical bone, in the trabecular bone, and in the total osseointegrated surface between the control (46.38 ± 16.17%) and saline (49.13 ± 11.52%) groups at 2 months was not statistically different ( p = 0.61). The total osseointegration areas of the control (53.98 ± 12.06%) and saline (51.40 ± 13.01%) groups at the 4 th month of the study were not statistically ( p = 0.61). Conclusion: Ingestion of salt did not affect directly the osseointegration process during the period of the experiment. The results suggest that mineral losses may not affect the achievement of good osseointegration in aging rats. (AU)


Assuntos
Animais , Masculino , Sódio na Dieta/efeitos adversos , Osseointegração/fisiologia , Envelhecimento , Densidade Óssea , Ratos Wistar
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(6): 1036-1041, 2019 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-31848500

RESUMO

OBJECTIVE: To observe the effect of methyl eugenol on the expression of aquaporin (AQP) 5 in nasal mucosa of rats with allergic rhinitis and to explore its significance. METHODS: In the study, 128 Wistar rats were randomly divided into normal control group, AR model control group, budesonide positive control group, 80 mg/kg group, 40 mg/kg group, 20 mg/kg group and 10 mg/kg group, and ovalbumin (OVA) was used to establish the model of allergic rhinitis. After successful modeling, castor oil, budesonide and corresponding doses of methyl eugenol were given respectively. After 1, 2 and 4 weeks of administration, the distribution of AQP5 in nasal mucosa was observed by immunohistochemistry. The expression of AQP5 in nasal mucosa of each group was compared by Western blotting. The expression of AQP5 mRNA was compared with real-time PCR. RESULTS: AQP5 was mainly located in the glandular epithelium and ductal epithelial cell membrane and cytoplasm. The expression of AQP5 and AQP5 mRNA in nasal mucosa of the rats in the model control group was lower than that in the normal control group (P<0.05). AQP5 and AQP5 mRNA in nasal mucosa of the rats in each treatment group were higher than those in the model control group in varying degrees. The expression of AQP5 in the budesonide group was not significantly different from that in the normal control group 1, 2 and 4 weeks after drug intervention (P>0.05), but there was significant difference between the budesonide group and the model control group (P<0.05). The expression of AQP5 mRNA in the budesonide group was significantly different from that in the normal control group and the model control group (P<0.05).After 2 weeks of intervention, the expression of AQP5 in each dose group of methyleugenol was not significantly different from that in the budesonide group (P>0.05). After 1 week of intervention, there was no significant difference in AQP5 mRNA between the 20 mg/kg group and the normal control group (P>0.05), but there was significant difference between the 20 mg/kg group and the model control group (P<0.05). CONCLUSION: Methyl eugenol may increase the degree of edema of the nasal mucosa by reducing the expression of AQP5 and reduce the secretion of glands, thus alleviating the symptoms of allergic rhinitis, sneezing and runny nose.


Assuntos
Rinite Alérgica , Animais , Aquaporina 5 , Eugenol/análogos & derivados , Mucosa Nasal , Ratos , Ratos Wistar
10.
J Contemp Dent Pract ; 20(10): 1146-1150, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883248

RESUMO

AIM: At the moment there is no clear evidence with clinico-histological and immunohistochemical studies in animals to show the curcumin effect on the gingival overgrowth following phenytoin consumption. The purpose of the present study was to identify this subject. MATERIALS AND METHODS: In this experimental study, 50 adult male Wistar rats were divided into three groups. The rats in groups I and II received 100 mg/kg of phenytoin per day. Group II also received 20 mg/kg intraperitoneal curcumin per day. The control group received the curcumin vehicle only. Gingival clinical dimensions were measured at the beginning and end of the study. The rats were then sacrificed, biopsy of gingiva was prepared, and the samples were stained with hematoxylin-eosin. Morphometry was performed to evaluate the degree of inflammation, epithelial thickness, number, and cross-sectional area of the blood vessels. Immunohistochemical staining was performed using Ki67 and α-SMA. RESULTS: Compared to the control group, Phenytoin in group I increased gingival volume. There was significance difference in group II with group I and control after intervention in the clinical view (p = 0.002). The difference in the number of blood vessels between groups I and II was statistically significant (p = 0.001). Significant differences were observed in blood vessel cross-sectional area (p = 0.001), epithelial thickness (p = 0.002), Ki67, and α-SMA expression between groups I and II (p = 0.001). CONCLUSION: In rats, curcumin seems to exerts its effects in preventing an increase in gingival volume caused by Phenytoin through decreasing the inflammatory infiltration, decreasing the number of blood vessels and increasing their cross-sectional area, decreasing the thickness of the epithelium, and decreasing the expression of Ki67 and α-SMA. CLINICAL SIGNIFICANCE: It is suggested that curcumin may be effective in treatment of gingival enlargement following Phenytoin consumption in future. Larger sample size and clinical trials study are recommended. How to cite this article: Eftekharian S, Seifi S, Satari FD, et al. Curcumin Effect on the Prevention of Gingival Overgrowth Following Phenytoin Consumption in Rats: A Clinicohistological and Immunohistochemical Study. J Contemp Dent Pract 2019;20(10):1146-1150.


Assuntos
Curcumina , Crescimento Excessivo da Gengiva , Animais , Gengiva , Masculino , Fenitoína , Ratos , Ratos Wistar
11.
Indian J Dent Res ; 30(5): 708-715, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31854361

RESUMO

Introduction: Mucositis is a common complication in around 40% of patients receiving chemotherapy which profoundly impact the quality of life. Despite the availability of many therapeutic agents that claim to prevent or reduce the severity of oral mucositis, no intervention that is completely successful at preventing oral mucositis exists. The present study aimed to demonstrate the effect of local honey on methotrexate-induced mucositis of the tongue. Materials and Methods: The study was done in albino rats (n = 24), divided into four groups: honey-normal saline group (H/NS), distilled water-NS group (DW/NS), DW-methotrexate group (DW/MTX), and H/MTX group. Local honey was given (2.5 g/kg) twice a daily for 8 days. NS or methotrexate (60 mg/kg) interrupted the experiment procedure on day 4. At day 8, rats were sacrificed and middle third of tongue was removed for preparation of histological slides. Slides were examined for inflammatory cell infiltration (ICI), cell vacuolization (CV), congested blood vessels (CBV), thickness of epithelium (both dorsal and ventral mucosa), and thickness keratin. Results: Statistically significant association was found between the groups for ICI and CV, χ2 (3) = 11.97, P= 0.003 for ICI, and χ2 (3) = 8.307, P= 0.023 for CV. Mean number of CBV per microscopic filed was 0.445, 0.389, 1.28, and 0.5 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. Mean value of dorsal epithelial thickness (µm) was 96.78 ± 13.59, 100.50 ± 9.75, 75.53 ± 9.24, and 98.75 ± 10.92 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. Mean value of ventral epithelial thickness (µm) was 70.45 ± 13.60, 58.38 ± 14.26, 37.04 ± 5.37, and 52.80 ± 7.97 for H/NS, DW/NS, DW/MTX, and DW/H groups, respectively. The thickness of epithelium of DW/MTX group was significantly different from other groups (P < 0.05). Conclusion: The present study demonstrated the palliative effect of local honey over the mucositis induced by the chemotherapeutic drug (methotrexate).


Assuntos
Mel , Mucosite , Animais , Abelhas , Inibidores Enzimáticos , Humanos , Qualidade de Vida , Ratos , Ratos Wistar , Tetra-Hidrofolato Desidrogenase
12.
Rev. Esc. Enferm. USP ; 53: e03487, Jan.-Dez. 2019. tab, graf
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1020392

RESUMO

RESUMO Objetivo Avaliar o efeito da Justicia acuminatissima , Sara Tudo do Amazonas, na função renal, na hemodinâmica renal, no perfil oxidativo e na histologia renal em ratos com injúria renal aguda isquêmica. Método Ensaio pré-clínico com ratos Wistar, adultos, machos (250-350 g), distribuídos nos grupos Sham, Isquemia e Isquemia + Sara Tudo. Foram avaliados os parâmetros hemodinâmicos, a função renal, o estresse oxidativo e a histologia renal. Resultados O pré-tratamento com o Sara Tudo atenuou a lesão funcional, o que foi evidenciado pelo aumento no clearance de creatinina, redução dos marcadores oxidativos e elevação de tióis, pela melhora significativa do fluxo sanguíneo renal, diminuição da resistência vascular renal e redução da lesão tubulointersticial no tecido renal. Conclusão A renoproteção da Justicia acuminatissima , Sara Tudo, na injúria renal aguda isquêmica, caracterizou-se por melhora significativa da função renal, reduzindo a lesão oxidativa, com impacto positivo na histologia renal.


RESUMEN Objetivo Evaluar el efecto de la planta Justicia acuminatissima , "Sana Todo del Amazonas", en la función renal, la hemodinámica renal, el perfil oxidativo y la histología renal en ratones con injuria renal aguda isquémica. Método Ensayo pre clínico con ratones Wistar, adultos, machos (250-350 g), distribuidos en los grupos Sham, Isquemia e Isquemia + Sana Todo. Fueron evaluados los parámetros hemodinámicos, la función renal, el estrés oxidativo y la histología renal. Resultados El pre tratamiento con el Sana Todo atenuó la lesión funcional, lo que fue evidenciado por el aumento en el aclaramiento de creatinina, reducción de los marcadores oxidativos y elevación de tioles, por la mejora significativa del flujo sanguíneo renal, disminución de la resistencia vascular renal y reducción de la lesión tubulointersticial en el tejido renal. Conclusión La renoprotección de la Justicia acuminatissima , "Sana Todo del Amazonas", en la injuria renal aguda isquémica se caracterizó por mejora significativa de la función renal, reduciendo la lesión oxidativa, con impacto positivo en la histología renal.


ABSTRACT Objective To evaluate the effects of Justicia acuminatissima , or Amazonian Sara Tudo , on renal hemodynamics, oxidative profile, and renal histology in rats with ischemic acute kidney injury. Method Preclinical assay with adult male Wistar rats, weighing from 250 g to 350 g, distributed into Sham, ischemia, and ischemia + Sara Tudo groups. Hemodynamic parameters, renal function, oxidative stress, and renal histology were evaluated. Results Pretreatment with Sara Tudo reduced the functional injury, which was shown by the increase in creatinine clearance and thiols; reduction of oxidative markers, renal vascular resistance, and tubulointerstitial injury in the renal tissue; and the significant improvement in renal blood flow. Conclusion The renoprotection provided by Justicia acuminatissima , or Sara Tudo , in cases of ischemic acute kidney injury was characterized by a marked improvement in renal function, reducing the oxidative injury, and impacting on renal histology positively.


Assuntos
Ratos , Reperfusão , Medicamentos Fitoterápicos , Lesão Renal Aguda , Terapias Complementares , Ratos Wistar , Experimentação Animal
13.
Zhen Ci Yan Jiu ; 44(12): 898-905, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31867910

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on inflammatory reaction and insulin sensitivity in insulin-resistant obese (OIR) rats. METHODS: Thirteen male Wistar rats were randomly selected as the control group and fed with common diet. The other 39 rats were fed with high-fat diet for 8 weeks to establish OIR model and then randomized into model, EA and sham EA groups. EA (2 Hz, 1 mA) was applied to unilateral "Zusanli" (ST36), "Fenglong" (ST40), "Zhongwan" (CV12) and "Guanyuan" (CV4) for 15 min, once every other day for 8 weeks, and sham EA was applied to unilateral 4 control spots about 5 mm lateral to the aforementioned 4 acupoints after shallowly inserting acupuncture needles, but without electric current output. After 8 weeks' intervention, the body weight was recorded and the glucose infusion rate (GIR) measured using hyperinsulinemic-euglycemic clamp technique. At the 6th week of intervention, glucose contents of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tole-rance test (IPITT) were measured. The levels of serum insulin (INS) and inflammatory factors as C-reactive protein (CRP), IL-6 and TNF-α were measured by using ELISA at the end of the treatment. The expression levels of IL-6, TNF-α, monocyte chemoattractant protein-1(MCP-1), IL-10 and IL-1ß proteins and mRNAs in the abdominal adipose tissues were detected by Western blot and quantitative real time-PCR, separately. The CD68 expression (displaying infiltration of macrophages) of adipose tissue was detected using immunohistochemistry. RESULTS: After modeling, the contents of glucose of IPGTT at 30, 60 and 120 min and those of IPITT at 15, 30, 60 and 120 min, serum INS, CRP, IL-6 and TNF-α, as well as the expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein were significantly increased (P<0.01, P<0.05), while the levels of GIR and IL-10 protein and mRNA were obviously decreased in the model group in comparison with those of the control group (P<0.01), suggesting an increase of inflammation and a decline of INS sensitivity. Following the interventions, the increased contents of glucose of IPGTT and IPITT, serum INS, CRP, IL-6 and TNF-α, expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein, and the decreased levels of GIR and IL-10 protein and mRNA were evidently reversed in the EA group compared with the model group (P<0.01, P<0.05) rather than those in the sham EA group (P>0.05). CONCLUSION: EA can reduce the level of inflammation and improve insulin sensitivity in OIR rats.


Assuntos
Eletroacupuntura , Resistência à Insulina , Pontos de Acupuntura , Animais , Inflamação , Insulina , Masculino , Obesidade , Ratos , Ratos Wistar
14.
Chin J Physiol ; 62(5): 188-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670282

RESUMO

We explored the therapeutic potential of intragastric administration of traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung [ITG]) extract and its major component Daidzin on cyclophosphamide (CYP)-induced cystitis, oxidative stress, fibrosis, inflammation, and bladder hyperactivity in rats. Female Wistar rats were divided into control, CYP (200 mg/kg), CYP+ITG (1.17 g/kg/day), and CYP+Daidzin (12.5 mg/kg/day) groups. We measured the voiding function by the transcystometrogram and evaluated the pathology with the hematoxylin and eosin and Masson stain. We determined the bladder reactive oxygen species (ROS) amount by an ultrasensitive chemiluminescence analyzer, the expression of 3-nitrotyrosine (3-NT) and NADPH oxidase 4 (NOX4) by Western blot and the expression of multiple cytokine profiles, including matrix metalloproteinase (MMP)-8 and tissue inhibitor of metalloproteinase (TIMP)-1 through a cytokine array. ITG extract contains 1.07% of Daidzin through high-performance liquid chromatography. The effect of ITG extract and Daidzin in scavenging hydrogen peroxide activity was more efficient than distilled water. CYP-induced higher urination frequency, shorter intercontraction interval, and lower maximal voiding pressure in the bladders and these symptoms were significantly ameliorated in CYP+ITG and CYP+Daidzin groups. The amount of in vivo bladder ROS and the expression of 3-NT and NOX4 expressions were significantly increased in CYP group but were efficiently decreased in the CYP+ITG and CYP+Daidzin groups. CYP-induced fibrosis, hemorrhage, leukocyte infiltration, and edema in the bladders were significantly attenuated in the CYP+ITG and CYP+Daidzin groups. These results suggested that ITG extract and its active component Daidzin effectively improved CYP-induced oxidative stress, inflammation, and fibrosis through inhibiting the MMP-8, TIMP-1, and oxidative stress.


Assuntos
Cistite , Animais , Ciclofosfamida , Feminino , Fibrose , Glicina , Inflamação , Isoflavonas , Estresse Oxidativo , Extratos Vegetais , Ratos , Ratos Wistar
15.
Adv Clin Exp Med ; 28(10): 1429-1436, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31670915

RESUMO

BACKGROUND: Hirschsprung's disease-associated enterocolitis (HE) is a life-threatening septic complication of Hirschsprung's disease (HD), leading to bacterial translocation (BT) and sepsis. Many factors, such as intestinal stasis, HD-related inherited immune disorders and abnormal mucosal secretion have been implicated in its pathogenesis. OBJECTIVES: To investigate the effect of intestinal stasis as an independent factor in the pathogenesis of HE intestinal lesions and its systematic effects. MATERIAL AND METHODS: The rectal ganglion cells of 46 Wistar rats were chemically ablated through local benzalkonium chloride (BAC) injection, in order to create a HD model (megacolon rats) that does not carry the possible genetic burden of HD. The animals were sacrificed either on the 20th or 25th day after ablation and were examined for histopathological changes on the wall of the small intestine, presence of bacterial translocation in body organs, body biometrics, and white blood cell count (WBC) and hemoglobin concentration. The results were compared to control animals. RESULTS: In the megacolon rats, severe damage on the small intestine as well as BT proportional to the extent of the intestinal damage and to the time elapsed after ablation was observed. Significant effects on the WBCs, hemoglobin concentration and biometric parameters were also observed. CONCLUSIONS: In megacolon rats, intestinal stasis can lead by itself to a full-blown HE. The HE lesions that promote BT are present even in regions distant from the aganglionic bowel and are proportional to the time elapsed under the influence of intestinal stasis. Systematic effects such as growth retardation are also produced.


Assuntos
Enterocolite , Doença de Hirschsprung/patologia , Obstrução Intestinal , Megacolo/complicações , Animais , Translocação Bacteriana , Modelos Animais de Doenças , Enterocolite/diagnóstico , Enterocolite/etiologia , Intestinos/microbiologia , Megacolo/patologia , Ratos , Ratos Wistar , Sepse
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 293-296, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701708

RESUMO

OBJECTIVE: To investigate the effects of vitamin E on the respiratory function impairment in rats with chronic obstructive pulmonary disease (COPD) after exposed to high temperature and PM2.5. METHODS: Fifty-four 7-week-old SPF male Wistar rats were randomly divided into 9 experimental groups (n=6). The rat COPD model was established by lipopolysaccharide (LPS) and smoke exposure. After modeled, the rats were tracheal instilled with PM2.5 (0 mg/ml, 3.2 mg/ml) and intraperitoneally injected with vitamin E at the dose of 40 mg/kg (20 mg/ml). Part of rats (high temperature groups) were then exposed to high temperature (40℃), once (8 h) a day for three consecutive days. After the last exposure, the lung function of rats was detected. The expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were detected by corresponding ELISA kits. RESULTS: Compared with the control group, exposure of high temperature and PM2.5 could inhibit the lung function of COPD rats significantly (P<0.05); the level of MCP-1 was increased significantly in PM2.5-exposure groups (P<0.05); iNOS was increased significantly in the groups of high temperature (P<0.05). Compared with the single-PM2.5 exposure groups, TNF-α in lung was decreased in the normal temperature health group and high temperature COPD group (P<0.05) after treated with vitamin E; MCP-1 was decreased in all vitamin E-treated groups (P<0.05); the decreased iNOS only appeared in the group of high temperature with vitamin E treatment. CONCLUSION: High temperature and PM2.5 could aggravate the inflammation of COPD rats. As an antioxidant, vitamin E may protect the lung from the damage effects.


Assuntos
Temperatura Alta/efeitos adversos , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Vitamina E/farmacologia , Animais , Quimiocina CCL2/metabolismo , Pulmão/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 359-362, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701723

RESUMO

OBJECTIVE: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. METHODS: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1ß), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. RESULTS: Compared to sham group, the escape latency in VCI group was significantly extended (P<0.01) and the times of passing through the platform were decreased remarkably (P<0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P<0.01), while the contents of MDA, TNF-α, IL-1ß and MAO were increased remarkably (P<0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P<0.01, P<0.05) and the times of passing through the platform were increased remarkably (P<0.01, P<0.05), the levels of SOD, GSH and 5-HT were increased significantly (P<0.01), while the contents of TNF-α, IL-1ß and MAO were decreased remarkably (P<0.01). CONCLUSION: Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.


Assuntos
Berberina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Hipocampo , Inflamação , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar
18.
Vestn Oftalmol ; 135(5. Vyp. 2): 160-170, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31691655

RESUMO

PURPOSE: To investigate the toxic effects of frequent instillations of anti-infective solutions (antibiotic eye drops - 0.3 and 1.4% tobramycin, 0.5% levofloxacin and 0.5% moxifloxacin; antiseptic eye drops - 0.05% pyloxidine and 0.025% chlorhexidine; antifungal drug - 2 mg/ml fluconazole solution) on ocular tissues. MATERIAL AND METHODS: The study was conducted on 21 Wistar rats (42 eyes) using method of semi-fine sections. RESULTS: The majority of antibiotics and antifungal agents do not cause toxic reactions in rats` eyes when instilled with frequent regimen with the exception of 'fortified' 1.4% tobramycin and pyloxidine solutions, which caused a decrease in corneal endothelial cells density and formation of fibrovascular tissue in the anterior chamber. CONCLUSION: Frequent instillations of antimicrobial drug solutions is a safe method for the treatment of purulent corneal ulcers and purulent keratitis. The exceptions were solutions of 'fortified' 1.4% tobramycin and piloxidine (vitabact).


Assuntos
Anti-Infecciosos/uso terapêutico , Infecções Oculares Bacterianas , Animais , Antibacterianos , Cefazolina , Células Endoteliais , Soluções Oftálmicas , Ratos , Ratos Wistar
19.
J Photochem Photobiol B ; 201: 111634, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715551

RESUMO

Skin Flap is used in reconstructive plastic surgery. However, complications such as ischemia followed by local necrosis may occur, requiring a new surgical procedure. It is well known that photobiomodulation therapy (PBMT) is an effective technique for improving microcirculation and neoangiogenesis, which contributes positively to the blood supply in the pre and post surgical period. Thus, the objective of the present study was to investigate the effects of preemptive treatment with laser PBMT with different energies on the viability in skin flaps in rats. Sixty-three Wistar rats, male, were randomized into five groups: Control Group (CG) (n = 15): PBMT simulation; Preemptive group 1.1 J laser (GP1) (n = 15): preemptive laser PBMT with 1.1 J of energy per point; Preemptive group 4 J laser (GP4) (n = 15): preemptive PBMT with 4 J of energy per point; Laser group 11 J (G1) (n = 9): PBMT immediately after surgery with 1.1 J of energy per point; Laser group 4 J (G4) (n = 9): TFMB immediately after surgery with 4 J of energy per point. The CG, GP1 and GP4 groups started treatment 72 h prior to surgery and were subdivided into two experimental periods, one of them on the day of the flap and the other along with the other groups on the seventh postoperative day. Three days after the randomization, the animals underwent random skin flap surgery. PBMT was performed with a 660 nm laser at three points. In the first experimental period, a greater number of vessels were found, as well as mast cells in GP1 compared to the CG and greater expression of fibroblast growth factor and vascular endothelial growth factor in the GP1 and GP4 groups compared to the CG. In the second experimental period, GP1 presented a lower percentage of necrotic tissue, a higher number of vessels and a percentage of cells labeled with both VEGF and hypoxia indicible factor alpha (HIF-1α) compared to the CG, FGF in GP1, GP4 and G4 when compared to the CG. Thus, it was concluded that preemptive treatment with PBMT with the application of 1.1 J of energy per point is effective in improving the viability of the skin flap.


Assuntos
Lasers Semicondutores , Retalhos Cirúrgicos/patologia , Animais , Vasos Sanguíneos/patologia , Vasos Sanguíneos/efeitos da radiação , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/metabolismo , Mastócitos/efeitos da radiação , Necrose , Distribuição Aleatória , Ratos , Ratos Wistar , Retalhos Cirúrgicos/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Biochemistry (Mosc) ; 84(9): 1085-1092, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31693468

RESUMO

Many motor disorders are associated with depolarization of the membrane of skeletal muscle fibers due to the impaired functioning of Na,K-ATPase. Here, we studied the role of ouabain (specific Na,K-ATPase ligand) and AMP-activated protein kinase (key regulator of muscle metabolism) in the maintenance of muscle electrogenesis; the levels of these endogenous factors are directly related to the motor activity. After 4-day intraperitoneal administration of ouabain (1 µg/kg daily), a hyperpolarization of sarcolemma was registered in isolated rat diaphragm muscles due to an increase in the electrogenic activity of Na,K-ATPase. In acute experiments, addition of nanomolar ouabain concentrations to the bathing solution resulted in the muscle membrane hyperpolarization within 15 min. The effect of ouabain reversed to membrane depolarization with the increase in the external potassium concentration. It is possible that Na,K-ATPase activation by ouabain may be regulated by such factors as specific subcellular location, interaction with molecular partners, and changes in the ionic balance. Preventive administration of the AMP-activated protein kinase activator AICAR (5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside; 400 mg/kg body weight daily for 7 days) in chronic experiments resulted in the stabilization of the endplate structure and abolishment of depolarization of the rat soleus muscle membrane caused by the motor activity cessation. The obtained data can be useful for creating approaches for correction of muscle dysfunction, especially at the early stages, prior to the development of muscle atrophy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Potenciais de Ação/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Ouabaína/administração & dosagem , Ouabaína/farmacologia , Aminoimidazol Carboxamida/administração & dosagem , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Masculino , Fibras Musculares Esqueléticas/enzimologia , Fibras Musculares Esqueléticas/metabolismo , Ratos , Ratos Wistar , Ribonucleotídeos/administração & dosagem , Ribonucleotídeos/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Relação Estrutura-Atividade
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