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1.
Int. j. morphol ; 41(2): 625-633, abr. 2023. ilus, tab
Article in English | LILACS | ID: biblio-1440306

ABSTRACT

SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.


La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.


Subject(s)
Animals , Rats , Reperfusion Injury/drug therapy , Anthraquinones/administration & dosage , Kidney Diseases/drug therapy , Anti-Inflammatory Agents/administration & dosage , Dendritic Cells/drug effects , Reperfusion Injury/immunology , Signal Transduction , NF-kappa B/metabolism , Anthraquinones/immunology , Apoptosis/drug effects , Oxidative Stress , Toll-Like Receptor 4/metabolism , Interleukin-1beta/metabolism , Flow Cytometry , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammation , Injections, Intraperitoneal , Kidney Diseases/immunology
2.
Rev. chil. endocrinol. diabetes ; 16(3): 46-52, 2023. tab, ilus
Article in Spanish | LILACS | ID: biblio-1451956

ABSTRACT

El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.


The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.


Subject(s)
Animals , Male , Mice , Diet/adverse effects , Exenatide/administration & dosage , Obesity/etiology , Obesity/metabolism , Oxidation-Reduction , Blotting, Western , Muscle, Skeletal/metabolism , Thermogenesis , Fatty Acids/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Uncoupling Protein 2 , Irinotecan , Injections, Intraperitoneal , Mice, Inbred C57BL
3.
Rev. Ciênc. Méd. Biol. (Impr.) ; 21(1): 40-45, maio 05,2022. fig
Article in Portuguese | LILACS | ID: biblio-1370563

ABSTRACT

Introduction: dengue is a most common mosquito-borne viral disease in the Americas and tropical countries. Objective: in this work, mice were hyperimmunized with DENV 4 antigen to produce monoclonal antibodies (mAbs). Methodology: DENV 4 (GenBank KC806069) was inoculated in C6/36 cell monolayers cultivated in Leibovitz's 15 medium supplemented with 5% fetal bovine serum and incubated at 28 oC. The virus stock was submitted to concentration and ultracentrifugation and stored at -80 oC until use (VC DENV 4). Balb/c mice were injected intraperitoneally with 50µg of DENV-4 and successive intraperitoneal injections of 25 µg of VCDENV 4 with Freund's incomplete adjuvant were performed. The spleen cells were fused to SP2/0 myeloma cells with PEG 1540 and distributed in 96-well microplates with Iscove's modified medium with Hipoxantina­Aminopterina­Timidina. Hybridoma screening by indirect ELISA showed positive results for six mAbs, and their characterization was performed by Western blotting and Indirect Immunofluorescence (IFI) techniques. Results: the six mAbs showed strong recognition of prM (24/29 kDa), and minor reaction to E protein (66 kDa), E/E protein dimer (105 kDa), and NS1 (49 kDa) protein in two mAbs. The use of mAbs anti-prM as a diagnostic tool using IFI has been demonstrated to detect DENV-4 antigen in infected cells or tissues. Conclusion: DENV 4 generate mAbs with strong reactivity to prM with potential use to confirm the presence of DENV 4 antigen in tissues or infected cells.


Introdução: a dengue é uma doença viral transmitida por mosquitos comumente das Américas e países tropicais. Objetivo: neste trabalho, camundongos foram hiperimunizados com antígeno DENV 4 para produzir anticorpos monoclonais (mAbs). Metodologia: DENV 4 (GenBank KC806069) foi inoculado em monocamadas de células C6 / 36 cultivadas em meio Leibovitz 15 suplementado com 5% de soro fetal bovino e incubadas a 28oC. O estoque viral foi submetido à concentração, ultracentrifugação e armazenado a -80 oC (VC DENV 4). Camundongos Balb / c foram injetados intraperitonealmente com 50 µg de VC DENV-4 e injeções intraperitoneais sucessivas de 25 µg de antigeno com adjuvante incompleto de Freund. As células do baço foram misturadas a células SP2/0 com PEG 1540 e distribuídas em microplacas de 96 poços com meio Iscove Modificado em presença de Hipoxantina ­ Aminopterina ­ Timidina. A triagem de hibridomas por ELISA indireto apresentou resultados positivos para seis mAbs, e sua caracterização foi realizada por técnicas de Western blotting e Imunofluorescência Indireta (IFI). Resultados: os seis mAbs mostraram forte reconhecimento de prM (24/29 kDa) e reação menor à proteína E (66 kDa), dímero de proteína E / E (105 kDa) e proteína NS1 (49 kDa) em dois mAbs. O uso de mAbs anti-prM como uma ferramenta de diagnóstico utilizando IFI demonstrou eficacia em detectar o antígeno DENV-4 em células ou tecidos infectados. Conclusão: o mAbs produzidos para DENV 4 demonstraram uma forte reatividade contra prM, e poderiam ser uma ferramenta de uso potencial no diagnóstico de DENV 4 .


Subject(s)
Animals , Mice , Dengue/immunology , Dengue Virus/immunology , Antibodies, Monoclonal/biosynthesis , Antigens, Viral/administration & dosage , Injections, Intraperitoneal , Mice, Inbred BALB C
4.
Int. j. morphol ; 38(4): 1003-1009, Aug. 2020. tab, graf
Article in English | LILACS | ID: biblio-1124889

ABSTRACT

This study was set to investigate the effect of gum Arabic (G.A.) on diabetic kidney disease. We divided sixty male Sprague rats randomly into six groups. Normal control, normal rats treated with G.A., untreated diabetic rats, diabetic rats treated with insulin, diabetic rats treated with G.A., and diabetic rats treated with both insulin and G.A. Diabetes was induced by a single intraperitoneal injection of STZ. Forty eight hr post injections. Insulin was injected subcutaneously (1.6/IU/100g/day). We provided G.A. in drinking water (10 %w/ v).). At the end of the twelve weeks, blood was drawn for measurement of blood glucose, glycosylated hemoglobin (HbA1C), serum lipids, serum creatinine, and blood urea. Renal tissue oxidative stress (O.S.) was assessed by measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA). For histological assessments, sections from segments of kidneys were processed and stained with hematoxylin and eosin (H&E) for assessment under the light microscope. STZinduced diabetes caused an elevation of blood glucose, HbA1c, urea and creatinine, triglycerides LDL and cholesterol, MDA with reduction of HDL, GSH level, and CAT and SOD activities. Histologically, kidneys from diabetic rats showed marked glomerular and tubular changes. Administration of G.A. alone to diabetic rats had a significant hypoglycemic, hypolipidemic, and antioxidant effect, although the levels achieved remained significantly abnormal compared with the untreated group with no effect on urea and creatinine levels. Co-administration of G.A. with insulin reversed the impact of D.M. on all parameters evaluated including the histological changes and led to normal urea and creatinine levels. We concluded that G.A., in combination with insulin, improves chemically-induced diabetes and its renal complications, possibly by modulation of oxidative stress.


En este estudio se evaluó el efecto de la goma arábiga (GA) en la enfermedad renal diabética. Dividimos sesenta ratas macho Sprague Dawley al azar en seis grupos. Control normal, ratas normales tratadas con GA, ratas diabéticas no tratadas, ratas diabéticas tratadas con insulina, ratas diabéticas tratadas con GA y ratas diabéticas tratadas con insulina y GA. La diabetes fue inducida por una sola inyección intraperitoneal de STZ. Cuarenta y ocho horas después se inyectó insulina por vía subcutánea (1,6 / UI / 100 g / día). A los animales se les dió GA en agua potable (10 % p / v)). Al final de las doce semanas, se extrajo sangre para medir la glucosa, la hemoglobina glicosilada (HbA1C), los lípidos en suero, la creatinina en suero y la urea en sangre. El estrés oxidativo del tejido renal (SO) se evaluó midiendo las actividades de la enzima superóxido dismutasa (SOD) y la catalasa (CAT), y las concentraciones de glutatión reducido (GSH) y malondialdehído (MDA). Para las evaluaciones histológicas, se procesaron secciones de segmentos de riñones y se tiñeron con hematoxilina y eosina (H & E) para análisis bajo microscopio óptico. La diabetes inducida por STZ causó una elevación de la glucosa en sangre, HbA1c, urea y creatinina, triglicéridos LDL y colesterol, MDA con reducción de las actividades de HDL, GSH y CAT y SOD. Histológicamente, los riñones de ratas diabéticas mostraron marcados cambios glomerulares y tubulares. La administración de GA solo en las ratas diabéticas tuvo un efecto hipoglucémico, hipolipidémico y antioxidante significativo, aunque los niveles alcanzados permanecieron significativamente anormales en comparación con el grupo no tratado, sin ningún efecto sobre los niveles de urea y creatinina. La dministración conjunta de GA con insulina revirtió el impacto de DM en todos los parámetros evaluados, incluidos los cambios histológicos y condujeron a niveles normales de urea y creatinina. Concluimos que GA en combinación con insulina, mejora la diabetes inducida químicamente y sus complicaciones renales, posiblemente mediante la modulación del estrés oxidativo.


Subject(s)
Animals , Male , Rats , Diabetic Nephropathies/prevention & control , Gum Arabic/administration & dosage , Antioxidants/administration & dosage , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/pathology , Gum Arabic/pharmacology , Injections, Intraperitoneal , Kidney/drug effects , Antioxidants/pharmacology
5.
Braz. J. Vet. Res. Anim. Sci. (Online) ; 57(2): e166204, mai. 2020. ilus, graf
Article in English | VETINDEX, LILACS | ID: biblio-1122176

ABSTRACT

Medical management of abdominal abscesses in horses requires prolonged antibiotic therapy and presents varied success rates. A 6-year-old male horse with a history of colic and multiple abdominal punctures to relieve gas was attended. At admission, tachycardia, tachypnea, hyperthermia, mucosal congestion, dehydration, and rigid gait were observed. The association of physical examination, laboratory and ultrasonographic findings allowed the diagnoses of peritonitis and abdominal abscess. Supporting treatment plus broad spectrum antibiotic therapy was performed: daily intraperitoneal ceftriaxone (25 mg/kg, 7 days); daily intravenous gentamicin (6.6 mg/kg, 7 days); per os metronidazole three times a day (15 mg/kg 12 days), followed by the same dose twice a day (15 mg/kg 33 days), totaling 45 days of treatment. Plasma fibrinogen and ultrasonographic examination were the most effective tools to evaluate abscess evolution. There was normalization of the physical examination 24 h after beginning the treatment, consecutive regression of the nucleated cell count in the peritoneal fluid, and regression of plasma fibrinogen and size of the abscess. On the 10th treatment day, the animal was discharged from the hospital, maintaining oral therapy with metronidazole every 12 h (15 mg / kg). When the animal returned on the 30th day, an abscess size regression was observed. However, there was no resolution, and therapy with metronidazole was maintained. On the 45th day of treatment, a new hospital evaluation was performed, where the abscess resolved, and metronidazole was suspended. It is highlighted that the therapeutic association used in the treatment of abdominal infection and abscess resulted in a rapid clinical response.(AU)


O tratamento conservativo dos abscessos abdominais em equinos requer antibioticoterapia prolongada e apresenta variadas taxas de sucesso. Foi atendido um cavalo de seis anos de idade, com histórico de cólica e múltiplas punções abdominais por agulha para esvaziamento de gás. Na admissão, foram observados taquicardia, taquipnéia, hipertermia, congestão mucosa, desidratação e marcha rígida. A associação do exame físico, achados laboratoriais e ultrassonográficos permitiu o diagnóstico de peritonite e abscesso abdominal. Foi realizado tratamento suporte e antibioticoterapia de amplo espectro: ceftriaxona intraperitoneal diária (25 mg/kg, 7 dias); gentamicina intravenosa diária (6,6 mg/kg, 7 dias); metronidazol oral três vezes ao dia (15 mg/kg, 12 dias), seguido de mesma dose duas vezes ao dia, por mais 33 dias, totalizando 45 dias de tratamento. O fibrinogênio plasmático e o exame ultrassonográfico foram os recursos mais eficazes para a avaliação da evolução do abscesso. Após 24 horas do início do tratamento foi constatada a normalização do exame fisico, regressão progressiva da contagem de células nucleadas no líquido peritoneal, do fibrinogênio plasmático e do tamanho do abscesso. No 10° dia de tratamento o animal recebeu alta hospitalar, mantendo-se a terapia oral com metronidazol a cada 12 horas (15 mg/Kg). Em retorno, ao 30° dia, observou-se regressão do tamanho do abscesso, entretanto, não houve resolução, tendo sido mantida a terapia com metronidazol. No 45º dia de tratamento, realizou-se nova avaliação hospitalar, onde foi observada a resolução do abscesso e a admnistração do metronidazol foi suspensa. Destaca-se, que a associação terapêutica utilizada no tratamento de infecção abdominal e abscesso resultou em rápida resposta clínica.(AU)


Subject(s)
Animals , Peritonitis/veterinary , Ceftriaxone/administration & dosage , Gentamicins/administration & dosage , Abdominal Abscess/veterinary , Horses , Metronidazole/administration & dosage , Ultrasonics , Fibrinogen , Injections, Intraperitoneal/veterinary
6.
Diabetes & Metabolism Journal ; : 158-172, 2020.
Article in English | WPRIM | ID: wpr-811139

ABSTRACT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.METHODS: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.RESULTS: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).CONCLUSION: FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.


Subject(s)
Animals , Mice , Connective Tissue Growth Factor , Diabetes Mellitus, Type 1 , Diabetic Nephropathies , Epithelial-Mesenchymal Transition , Fibroblast Growth Factors , Fibroblasts , Fibrosis , Hypertrophy , Injections, Intraperitoneal , Kidney , Phosphorylation , Streptozocin , Transforming Growth Factor beta , Tumor Suppressor Protein p53
7.
Asian Journal of Andrology ; (6): 184-191, 2020.
Article in English | WPRIM | ID: wpr-1009750

ABSTRACT

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg-1) on day 36 or a dose of 40 mg kg-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.


Subject(s)
Animals , Male , Mice , Adult Germline Stem Cells/transplantation , Azoospermia/chemically induced , Busulfan/toxicity , Disease Models, Animal , Infertility, Male/chemically induced , Injections, Intraperitoneal , Spermatogenesis/drug effects , Spermatogonia/drug effects , Stem Cell Transplantation/methods
8.
Rev. Soc. Bras. Med. Trop ; 53: e20200016, 2020. tab, graf
Article in English | LILACS | ID: biblio-1101450

ABSTRACT

Abstract INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.


Subject(s)
Animals , Rats , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Tumor Necrosis Factor-alpha/blood , Sepsis/pathology , Oxidative Stress/drug effects , Etanercept/administration & dosage , Inflammation/prevention & control , Kidney/drug effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Rats, Sprague-Dawley , Sepsis/blood , Disease Models, Animal , Etanercept/pharmacology , Inflammation/pathology , Injections, Intraperitoneal
9.
Braz. j. otorhinolaryngol. (Impr.) ; 85(3): 267-274, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011617

ABSTRACT

Abstract Introduction: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. Objective: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Methods: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15 mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days. Cisplatin + gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day. A control group received 1 mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. Results: In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin + gallic acid group, this biochemical, histopathological and functional changes were reversed. Conclusion: In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.


Resumo Introdução: A cisplatina é um agente antineoplásico amplamente usado no tratamento de vários tipos de câncer. A ototoxicidade é um dos principais efeitos colaterais que restringem o uso da cisplatina. Objetivo: O objetivo deste estudo foi investigar a eficácia protetora do ácido gálico, em termos bioquímicos, funcionais e histopatológicos, contra a ototoxicidade induzida por cisplatina. Método: Vinte e oito ratas Sprague-Dawley foram incluídas. As ratas foram distribuídas aleatoriamente em quatro grupos de sete animais cada. O grupo cisplatina recebeu uma única dose intraperitoneal de 15 mg/kg de cisplatina. O grupo ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos. O grupo cisplatina + ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos e uma única dose intraperitoneal de 15 mg/kg de cisplatina no terceiro dia. O grupo controle recebeu 1 mL de solução salina via intraperitoneal por cinco dias consecutivos. Antes da administração do fármaco, todos os ratos foram expostos ao teste de emissões otoacústicas - produto de distorção. O teste foi repetido no sexto dia do estudo. Todos os ratos foram então sacrificados; as cócleas foram removidas e reservadas para análises bioquímicas e histopatológicas. Resultados: No grupo cisplatina, os valores da relação sinal-ruído do dia 6 foram significativamente mais baixos aos dos outros grupos. Além disso, os níveis de malondialdeído nos tecidos cocleares foram significativamente mais altos, e as atividades de superóxido dismutase e glutatione peroxidase foram significativamente mais baixas em comparação com o grupo controle. A avaliação histopatológica revelou erosão na estria vascular, degeneração e edema na camada de tecido conjuntivo em células endoteliais, comprometimento das células ciliadas externas e diminuição do número dessas células. No grupo cisplatina + ácido gálico, estas alterações bioquímicas, histopatológicas e funcionais foram revertidas. Conclusão: Tendo em vista os nossos achados, consideramos que o ácido gálico pode ter desempenhado um papel protetor contra a ototoxicidade induzida por cisplatina em ratas, conforme indicado pelos resultados do teste emissões otoacústicas - produto de distorção, achados bioquímicos e análises imuno-histoquímicas.


Subject(s)
Animals , Female , Rats , Cisplatin/toxicity , Otoacoustic Emissions, Spontaneous/drug effects , Cochlea/drug effects , Cochlea/pathology , Protective Agents/administration & dosage , Gallic Acid/administration & dosage , Acoustic Stimulation , Immunohistochemistry , Rats, Sprague-Dawley , Disease Models, Animal , Injections, Intraperitoneal
10.
Odovtos (En línea) ; 21(1): 53-66, Jan.-Apr. 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-1091471

ABSTRACT

Abstract 19. Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria. In animals, intraperitoneal administration of LPS, stimulates innate immunity and the production of proinflammatory cytokines. LPS provides an inflammatory stimulus that activates the neuroimmune and neuroendocrine systems resulting in a set of responses termed sickness behavior. The purpose of this protocol is to describe step-by-step the preparation and procedure of application of intraperitoneal injection of LPS in rats, as a guide for those researchers that want to use this assay to mount an inflammatory response. LPS intraperitoneal challenge in rats has been widely used to evaluate antiinflammatory reagents and to address basic scientific questions.


Resumen 23. El lipopolisacárido (LPS) es un componente de la membrana externa de las bacterias Gram negativas. En animales, la administración intraperitoneal de LPS estimula la inmunidad innata y la producción de citoquinas proinflamatorias. El LPS proporciona un estímulo inflamatorio que activa el sistema neuroinmunológico y el sistema neuroendocrino, lo que da como resultado un conjunto de respuestas denominadas conductas de enfermedad. El propósito de este protocolo es describir paso a paso la preparación y el procedimiento de aplicación de la inyección intraperitoneal de LPS en ratas, como una guía para aquellos investigadores que desean utilizar este método para estimular una respuesta inflamatoria en el animal. La estimulación con LPS en ratas, aplicada intraperitonealmente, se ha utilizado ampliamente para evaluar reactivos antiinflamatorios y para abordar preguntas básicas de investigación científica.


Subject(s)
Animals , Rats , Lipopolysaccharides/analysis , Injections, Intraperitoneal/methods , Endotoxins/analysis , Gram-Negative Bacteria
11.
Journal of Gynecologic Oncology ; : e59-2019.
Article in English | WPRIM | ID: wpr-764524

ABSTRACT

OBJECTIVE: Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS). METHODS: Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit. RESULTS: Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 µg/mL vs. Cmax=4.057 µg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 µg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054). CONCLUSIONS: We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01539785


Subject(s)
Female , Humans , Biopsy , Cisplatin , Cytoreduction Surgical Procedures , Diffusion , Disease-Free Survival , Drug Therapy , Endoscopy , Follow-Up Studies , Injections, Intraperitoneal , Minimally Invasive Surgical Procedures , Models, Animal , Ovarian Neoplasms , Pharmacokinetics , Plasma , Platinum , Prospective Studies , Recurrence
12.
Clinical Psychopharmacology and Neuroscience ; : 314-317, 2019.
Article in English | WPRIM | ID: wpr-763525

ABSTRACT

OBJECTIVE: Lurasidone is an antipsychotic drug that shows a relative lack of weight gain common to many antipsychotics. Aripiprazole and ziprasidone also show little weight gain and can reduce olanzapine-induced food intake and weight gain in animals, paralleling some clinical findings. We hypothesized that lurasidone would have similar actions. METHODS: Female Lister-hooded rats received intraperitoneal injection either 2× vehicle (saline), lurasidone (3 mg/kg) and vehicle, olanzapine (1 mg/kg) and vehicle, or olanzapine and lurasidone. Following drug administration food intake was measured for 60min. A further series of rats underwent a seven-day regime of once-daily administration of the above doses and free access to food and water. Weight gain over the course of the study was monitored. RESULTS: Olanzapine induced a significant increase in food intake while lurasidone showed no significant effect. Co-administration of lurasidone with olanzapine suppressed the increase in food intake. Repeated dosing showed an increase in body weight after seven days with olanzapine, and no significant effect observed with lurasidone, while repeated administration of lurasidone with olanzapine reduced the effect of olanzapine on the increase in body weight. CONCLUSION: These findings support our hypotheses in that lurasidone, in addition to a lack of effect on acute food intake and short term weight gain, can reduce olanzapine-induced food intake and weight gain in rats. This indicates the drug to have an active anti-hyperphagic mechanism, rather than solely the absence of a drug-induced weight gain that is such a severe limitation of drugs such as olanzapine.


Subject(s)
Animals , Female , Humans , Rats , Antipsychotic Agents , Aripiprazole , Body Weight , Eating , Injections, Intraperitoneal , Lurasidone Hydrochloride , Water , Weight Gain
13.
Laboratory Animal Research ; : 154-164, 2019.
Article in English | WPRIM | ID: wpr-786408

ABSTRACT

In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood–brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days. To elucidate the delivery efficiency of HSP70 into the hippocampus, western blot analysis for polyhistidine was conducted. Polyhistidine protein levels were significantly increased in control-HSP70- and Tat-HSP70-treated groups compared to the control or vehicle-treated group. However, polyhistidine protein levels were significantly higher in the Tat-HSP70-treated group compared to that in the control-HSP70-treated group. In addition, immunohistochemical study for HSP70 showed direct evidences for induction of HSP70 immunoreactivity in the control-HSP70- and Tat-HSP70-treated groups. Administration of Tat-HSP70 increased the novel object recognition memory compared to untreated mice or mice treated with the vehicle. In addition, the administration of Tat-HSP70 significantly increased the populations of proliferating cells and differentiated neuroblasts in the dentate gyrus compared to those in the control or vehicle-treated group based on the Ki67 and doublecortin (DCX) immunostaining. Furthermore, the phosphorylation of cAMP response element-binding protein (pCREB) was significantly enhanced in the dentate gyrus of the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. Western blot study also demonstrated the increases of DCX and pCREB protein levels in the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. In contrast, administration of control-HSP70 moderately increased the novel object recognition memory, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to that in the control or vehicle-treated group. These results suggest that Tat-HSP70 promoted hippocampal functions by increasing the pCREB in the hippocampus.


Subject(s)
Animals , Mice , Blotting, Western , Cell Membrane , Cell Proliferation , Cyclic AMP Response Element-Binding Protein , Dentate Gyrus , Heat-Shock Proteins , Hippocampus , Hot Temperature , HSP70 Heat-Shock Proteins , Injections, Intraperitoneal , Memory , Neurons , Phosphorylation
14.
Laboratory Animal Research ; : 107-113, 2019.
Article in English | WPRIM | ID: wpr-786397

ABSTRACT

Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.


Subject(s)
Animals , Humans , Male , Mice , Rats , Acetaminophen , Alanine Transaminase , Cell Death , Cytochrome P-450 CYP2E1 , Cytochromes , Glutathione , Injections, Intraperitoneal , Korea , Lipid Peroxidation , Liver , Malondialdehyde , Mice, Inbred ICR , Necrosis , Oxidative Stress
15.
Laboratory Animal Research ; : 132-139, 2019.
Article in English | WPRIM | ID: wpr-786394

ABSTRACT

Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 µg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.


Subject(s)
Adult , Animals , Humans , Male , Mice , Astrocytes , Body Weight , Cerebral Cortex , Cytokines , Glial Fibrillary Acidic Protein , Injections, Intraperitoneal , Microglia , Necrosis , Neuroglia , NF-kappa B , Oxidative Stress , Reactive Oxygen Species
16.
The Korean Journal of Pain ; : 79-86, 2019.
Article in English | WPRIM | ID: wpr-761690

ABSTRACT

BACKGROUND: The use of aroma oils dates back to at least 3000 B.C., where it was applied to mummify corpses and treat the wounds of soldiers. Since the 1920s, the term “aromatherapy” has been used for fragrance therapy with essential oils. The purpose of this study was to determine whether the essential oil of Eucalyptus (EOE) affects pain pathways in various pain conditions and motor coordination. METHODS: Mice were subjected to inhalation or intraperitoneal injection of EOE, and its analgesic effects were assessed by conducting formalin, thermal plantar, and acetic acid tests; the effects of EOE on motor coordination were evaluated using a rotarod test. To determine the analgesic mechanism, 5′-guanidinonaltrindole (κ-opioid antagonist, 0.3 mg/kg), naltrindole (δ-opioid antagonist, 5 mg/kg), glibenclamide (δ-opioid antagonist, 2 mg/kg), and naloxone (μ-opioid antagonist, 4, 8, 12 mg/kg) were injected intraperitoneally. RESULTS: EOE showed an analgesic effect against visceral pain caused by acetic acid (EOE, 45 mg/kg); however, no analgesic effect was observed against thermal nociceptive pain. Moreover, it was demonstrated that EOE did not have an effect on motor coordination. In addition, an anti-inflammatory effect was observed during the formalin test. CONCLUSIONS: EOE, which is associated with the μ-opioid pain pathway, showed potential effects against somatic, inflammatory, and visceral pain and could be a potential therapeutic agent for pain.


Subject(s)
Animals , Humans , Mice , Acetic Acid , Analgesics , Aromatherapy , Cadaver , Eucalyptus , Formaldehyde , Glyburide , Inhalation , Injections, Intraperitoneal , Military Personnel , Naloxone , Narcotic Antagonists , Nociceptive Pain , Oils , Oils, Volatile , Pain Measurement , Rotarod Performance Test , Visceral Pain , Wounds and Injuries
17.
Biomolecules & Therapeutics ; : 101-106, 2019.
Article in English | WPRIM | ID: wpr-719635

ABSTRACT

Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, 10⁻⁴ M). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine A1 receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an α₁-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular Ca²⁺ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.


Subject(s)
Animals , Humans , Rats , Acetylcholine , Atropine , Blood Glucose , Calcium Channels , Injections, Intraperitoneal , Muscle, Smooth , Papaverine , Prazosin , Protein Kinase C , Receptor, Adenosine A1 , Receptors, Muscarinic , Streptozocin , Type C Phospholipases , Urinary Bladder , Verapamil
18.
The Korean Journal of Physiology and Pharmacology ; : 161-169, 2019.
Article in English | WPRIM | ID: wpr-761787

ABSTRACT

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.


Subject(s)
Animals , Mice , Adipocytes , Adipogenesis , Aspergillus , Body Weight , Carrier Proteins , Diet, High-Fat , Glycerol , Injections, Intraperitoneal , Intra-Abdominal Fat , Lipase , Lipolysis , Lipoprotein Lipase , Mice, Obese , Peroxisomes , Rhizophoraceae , Sterol Esterase , Transcription Factors
19.
The Korean Journal of Parasitology ; : 117-125, 2019.
Article in English | WPRIM | ID: wpr-761730

ABSTRACT

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×10⁶ parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia-induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.


Subject(s)
Animals , Mice , Angiogenesis Inducing Agents , Hypoxia , Blood Vessels , Blotting, Western , Erythrocytes , Fluorescent Antibody Technique , Immunohistochemistry , Injections, Intraperitoneal , Malaria , Mortality , Parasitemia , Plasmodium , Plasmodium berghei , Vascular Endothelial Growth Factor A
20.
Chinese Journal of Traumatology ; (6): 161-165, 2019.
Article in English | WPRIM | ID: wpr-771617

ABSTRACT

PURPOSE@#To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1β by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury.@*METHODS@#Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups (n = 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 μg/kg (group D1) or 10 μg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation; the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1β were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups.@*RESULTS@#The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dose-dependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1β in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05).@*CONCLUSION@#Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1β are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury.


Subject(s)
Animals , Male , Dexmedetomidine , Pharmacology , Dose-Response Relationship, Drug , Hippocampus , Metabolism , Immunohistochemistry , Inflammasomes , Metabolism , Inflammation Mediators , Metabolism , Injections, Intraperitoneal , Interleukin-1beta , Metabolism , Laparotomy , Microglia , Metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Metabolism , Rats, Sprague-Dawley , Time Factors
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