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1.
Med Sci Monit ; 26: e920442, 2020 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-32198879

RESUMEN

BACKGROUND Notoginsenoside R1 (NR) is a major dynamic constituent of Panax notoginseng found to possess anti-inflammatory activity against various inflammatory diseases. However, its protective effects against renal ischemia-reperfusion (I/R) injury have not been elucidated. In male Wistar rats, we induced I/R under general anesthesia by occluding the renal artery for 60 min, followed by reperfusion and right nephrectomy. MATERIAL AND METHODS Rats were randomized to 4 groups: a sham group, an I/R group, an NR-pretreated (50 mg/kg) before I/R induction group, and an NR control group. All animals were killed at 72 h after I/R induction. Blood and renal tissues were collected, and histological and basic renal function parameters were assessed. In addition, levels of various kidney markers and proinflammatory cytokines were measured using RT-PCR, ELISA, and immunohistochemistry analysis. RESULTS After I/R induction, the onset of renal dysfunction was shown by the elevated levels of serum urea, creatinine levels, and histological evaluation, showing a 2-fold increase in the renal failure markers kim-1 and NGAL compared to control rats. Rats pretreated with NR before I/R induction had significantly better renal functions, with attenuated levels of oxidative markers, restored levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), tumor growth factor-ß1 (TGF-ß1), INF-γ, and IL-6, and increased anti-inflammatory cytokine levels (IL-10) compared to I/R-induced rats. CONCLUSIONS NR suppressed I/R-induced inflammatory cytokines production by suppressing oxidative stress and kidney markers, suggesting that NR is a promising drug candidate for prevention, progression, and treatment of renal dysfunction.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ginsenósidos/uso terapéutico , Inflamación/prevención & control , Daño por Reperfusión/prevención & control , Transducción de Señal/efectos de los fármacos , Animales , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Masculino , Nefrectomía , Distribución Aleatoria , Ratas , Ratas Wistar
2.
Zhen Ci Yan Jiu ; 45(1): 27-32, 2020 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-32144905

RESUMEN

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on silent information regulator 1 (SIRT1), forkhead transcription factor O1 (FoxO1), and proopiomelanocortin (POMC) in the hypothalamus of rats with high-fat diet-induced obesity (DIO), as well as the mechanism of EA in regulating central appetite peptides to help lose weight. METHODS: Male Wistar rats were randomly divided into normal group, model group, EA group, EA+inhibitor group, inhibitor group, and sham-operation group, with 10 rats in each group. High-fat diet was used to establish a rat model of DIO. The rats in the EA group and EA+inhibitor group were given EA at "Fenglong" (ST40), "Zhongwan "(CV12),"Guanyuan "(CV4), and"Zusanli" (ST36) with continuous wave at a frequency of 2 Hz and an intensity of 1 mA, for 10 minutes each time. The rats in the EA+inhibitor group and inhibitor group were given tube placement in the third ventricle and injection of the specific SIRT1 antagonist EX-527. The rats in the sham-operation group were given tube placement in the third ventricle and injection of artificial cerebrospinal fluid. The above treatment was given 3 times a week for 8 weeks in total. Body weight, food intake, and Lee's index were observed before and after treatment. An automatic biochemical analyzer was used to measure the serum levels of total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA), and Western blot was used to measure the protein expression of SIRT1, FoxO1, acetylated FoxO1(AC-FoxO1), and POMC in the hypothalamus. RESULTS: Before treatment, the model group, the EA group, the EA+inhibitor group, the inhibitor group, and the sham-operation group had significantly higher body weight and food intake than the normal group (P<0.01), and the model group and the sham-operation group had a significantly higher Lee's index than the normal group (P<0.05). Compared with the model group after treatment, the EA group and the EA+inhibitor group had significant reductions in body weight, food intake, TC, and the protein expression of AC-FoxO1 (P<0.01, P<0.05) and significant increases in the protein expression of SIRT1, FoxO1 and POMC (P<0.01, P<0.05); the EA group had significant reductions in Lee's index and the levels of TG, FFA(P<0.05,P<0.01);the inhibitor group had significant increases in food intake, the serum levels of TC, TG, FFA(P<0.01) and significant reductions in the protein expression of SIRT1, FoxO1 and POMC (P<0.01,P<0.05). Compared with the EA group, the EA+inhibitor group and the inhibitor group had significant increases in body weight, food intake, Lee's index, the levels of TG, FFA and the protein expression of AC-FoxO1 (P<0.01, P<0.05) and significant reductions in the protein expression of SIRT1, FoxO1 and POMC (P<0.01); the inhibitor group had significant increases in the serum levels of TC (P<0.01). Compared with the EA+inhibitor group, the inhibitor group had significant increases in body weight, food intake, the serum levels of TC, TG, FFA, and the protein expression of AC-FoxO1 (P<0.01), as well as significant reductions in the protein expression of SIRT1, FoxO1 and POMC (P<0.01). CONCLUSION: In rats with DIO, EA can effectively up-regulate the expression of SIRT1 in the hypothalamus, exert a deacetylation effect on FoxO1, and promote the expression of the downstream appetite-inhibiting peptide POMC, which may be one of the mechanisms of EA to help lose weight by regulating central appetite peptides in the obesity model.


Asunto(s)
Electroacupuntura , Proopiomelanocortina , Puntos de Acupuntura , Animales , Dieta Alta en Grasa , Hipotálamo , Masculino , Proteínas del Tejido Nervioso , Obesidad , Ratas , Ratas Wistar
3.
Zhen Ci Yan Jiu ; 45(2): 99-104, 2020 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-32144918

RESUMEN

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expression of liver protein kinase 1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and 6-phosphofructo-2-kinase (PFK2) in cardiomyocytes of rats with acute myocardial ischemia (AMI), so as to explore its mechanisms underlying cardioprotective effect. METHODS: Thirty male Wistar rats were randomly divided into sham-operation, model and EA pretreatment groups (n=10 rats per group). The AMI model was established by ligation of the left anterior descending branch of coronary artery. Before modeling, EA preconditioning (2 Hz/15 Hz, 1 mA) was applied to bilateral "Neiguan"(PC6) for 30 min, once daily for 14 days. Histopathological changes of myocardium was observed by microscope after H.E. staining. The level of lactate dehydrogenase (LDH) in serum was detected by ELISA. The expression of autophagy-associated proteins and mRNAs as LKB1, AMPKa1, AMPKa2 and PFK2 were detected by Western blot and real-time PCR, respectively. RESULTS: Compared with the sham-operation group, serum LDH content, and expression levels of myocardial AMPKa2 and PFK2 proteins and mRNAs were significantly up-regulated (P<0.01), and those of LKB1 and AMPKa1 proteins and mRNAs were increased in the model group (P<0.05). Following the intervention, serum LDH were apparently down-regulated (P<0.01), and expression levels of myocardial LKB1, AMPKa1 and PFK2 proteins and mRNAs were apparently up-regulated (P<0.01), but that of AMPKa2 protein and mRNA was remarkably down-regulated in the EA group (P<0.01). H.E. staining showed cell swelling, disordered arrangement of myocardial fibers with obvious rupture, interstitial bleeding and inflammatory infiltration, which was relatively milder in the EA preconditioning group. CONCLUSION: EA pretreatment can trigger LKB1/AMPK/PFK2 signaling pathway in AMI rats, which may contribute to its cardioprotective effect against ischemic myocardial injury by activating autophagy of cardiomyocytes. .


Asunto(s)
Electroacupuntura , Isquemia Miocárdica , Proteínas Quinasas Activadas por AMP , Puntos de Acupuntura , Animales , Masculino , Miocardio , Extractos Vegetales , Proteínas Serina-Treonina Quinasas , Ratas , Ratas Wistar , Transducción de Señal
4.
Science ; 367(6482): 1105-1112, 2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-32139538

RESUMEN

The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.


Asunto(s)
Núcleo Hipotalámico Dorsomedial/metabolismo , Conducta Social , Estrés Psicológico/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Animales , Emociones/fisiología , Femenino , Ácido Glutámico/metabolismo , Homeostasis , Masculino , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Prosencéfalo/metabolismo , Trastornos Psicofisiológicos/terapia , Ratas , Ratas Endogámicas LEC , Ratas Wistar , Transducción de Señal
5.
Braz Dent J ; 31(1): 57-62, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32159707

RESUMEN

The objective of this study was to investigate the effects of low-level laser therapy (LLLT) and cigarette smoke on alveolar socket osteoclastogenesis signaling after tooth extraction, in rats. Sixty male Wistar rats were randomly assigned to four groups with 15 animals each: Control Group (with right maxillary molar extraction - ME), Experimental I (with ME and LLLT), Experimental II (with ME and cigarette smoke) and Experimental III group (with ME, LLLT and cigarette smoke). Euthanasia was performed at 3, 7 and 14 days postoperative. qRT-PCR was used to evaluate expression of Tnfrsf11a (RANK), Tnfsf11 (Rankl) and Tnfrsf11b (OPG). Data were submitted to statistical analysis using two-way ANOVA followed by Bonferroni test (α=0.05). There was an upregulation of RANK, RANKL and OPG genes over all the time of healing in Exp I group compared to control group. Exp II group showed a decreased expression of all genes over time, whereas Exp III genes expression were higher than Exp II values but lower than Control and Exp I values over time. The results of this study concluded that the LLLT had a positive effect, whereas cigarette smoke had a negative effect on RANK, RANKL and OPG gene expression in bone remodeling process.


Asunto(s)
Fumar Cigarrillos , Terapia por Luz de Baja Intensidad , Animales , Masculino , Ratas , Ratas Wistar , Extracción Dental , Cicatrización de Heridas
6.
Bratisl Lek Listy ; 121(2): 164-169, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115972

RESUMEN

OBJECTIVE: Cerebrospinal fluid (CSF) contains proliferation, differentiation and maturation signals that are essential factors for brain development. Due to presence of such factors this fluid has proliferative and differentiation potential. A previous study showed that maternal sleep deprivation (MSD) decrease the number of newborn neurons in development of hippocampus. Also, it impairs hippocampus-dependent spatial learning and memory in the young offspring rat. MSD can change CSF factors. In the present study, the effect of MSD-CSF on differentiation of mesenchymal stem cells to neural cells was examined, and expression of Nestin, Neun, and NeurD1 that are neurogenic markers was investigated. MATERIAL AND METHODS: In this study, bone marrow mesenchymal stem cells were aspirated from the femur and tibia of young male Wistar rats. Then cell suspension was cultured in DMEM medium supplemented with 10 % FBS and 1 % antibiotics. Pregnant rats were subjected to sleep deprivation for 6 h by gentle handling during 4th, 7th, and 18th day of pregnancy. CSF was collected from cisterna magna of neonate rats. CSF was added to culture media with a 5 % ratio (v/v). Then cell viability was determined with MTT assay. Total cellular RNA was extracted, cDNA was synthesized and NeuN, Nestin, NeuroD1 and IL-6 genes were analyzed by Real-time PCR. RESULTS: Real time-PCR analysis showed that expression of Neun and NeurD1gene decreased compared with culture in normal CSF (N-CSF), and also showed that expression of Nestin did not decrease, inflammatory gene (IL-6) showed high expression compared to culture with N-CSF. CONCLUSION: Based on our results, MSD-CSF could inhibit neurogenesis process in mesenchymal stem cells and also, this result suggests that MSD can suppress neural differentiation and decrease of neurogenesis gene expression. Overall these findings suggest that insomnia and sleep loss may active inflammatory responses in the brain and change CSF-markers (Fig. 3, Ref. 34).


Asunto(s)
Encéfalo , Diferenciación Celular , Células Madre Mesenquimatosas , Privación de Sueño , Animales , Encéfalo/crecimiento & desarrollo , Células Cultivadas , Femenino , Masculino , Embarazo , Ratas , Ratas Wistar
7.
Bratisl Lek Listy ; 121(3): 235-241, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115983

RESUMEN

AIM: Hyperglycemia, oxidative stress and hyperlipidemia are features of diabetes mellitus. Thiamine has beneficial effects on carbohydrate metabolism and it was proposed that this vitamin has antihyperlipidemic and antioxidant effects. Our aim was to investigate the effects of thiamine on oxidative stress and metabolic changes in streptozotocin (STZ) induced diabetic rats. METHOD: Diabetes was induced by a single intraperitoneal injection of STZ. Thiamine (6 mg/kg) was added to drinking water for five weeks. The rats were divided into four groups: control rats; thiamine treated control rats; diabetic rats; thiamine treated diabetic rats. Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase (PON) and arylesterase (AE) activities were measured with spectrophotometric methods, and erythrocyte superoxide dismutase (SOD) and blood glutathione peroxidase (GSH-Px) activities were determined using commercial kits. RESULTS: Thiamine treatment reduced plasma and tissue MDA levels, serum glucose, total cholesterol and triglyceride levels, and increased serum high density lipoprotein- cholesterol and insulin levels, serum PON and AE, erythrocyte SOD and blood GSH-Px activities. CONCLUSION: Thiamine significantly improves oxidative stress and has hyperinsulinemic and antihyperlipidemic effects so we suggest that thiamine might be used as a supportive therapeutic agent in diabetes (Tab. 2, Fig. 3, Ref. 53).


Asunto(s)
Antioxidantes , Diabetes Mellitus Experimental , Estrés Oxidativo , Tiamina , Animales , Antioxidantes/farmacología , Glucemia , Malondialdehído , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa , Tiamina/farmacología
8.
Braz J Med Biol Res ; 53(3): e8761, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32159612

RESUMEN

Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.


Asunto(s)
Calcio/análisis , Inhibidores Enzimáticos/farmacología , Contracción Miocárdica/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Adiposidad , Animales , Peso Corporal/fisiología , Inhibidores Enzimáticos/administración & dosificación , Hemodinámica , Masculino , Modelos Animales , Actividad Motora/fisiología , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , NG-Nitroarginina Metil Éster/administración & dosificación , Óxido Nítrico Sintasa/metabolismo , Ratas Wistar , Presión Ventricular/efectos de los fármacos
9.
Rev Soc Bras Med Trop ; 53: e20190477, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32049205

RESUMEN

INTRODUCTION: Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model. METHODS: Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection. RESULTS: All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples. CONCLUSIONS: Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.


Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Nitroimidazoles/administración & dosificación , Parasitemia/tratamiento farmacológico , Triazoles/administración & dosificación , Tripanocidas/administración & dosificación , Enfermedad Aguda , Animales , ADN Protozoario , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Quimioterapia Combinada , Carga de Parásitos , Ratas , Ratas Wistar
10.
Life Sci ; 245: 117368, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32001270

RESUMEN

AIMS: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs. MAIN METHODS: An in vivo model of I/R injury was tested in control, mTOR+/+, and mTOR+/-. Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified. Biochemical and mitochondrial swelling assays were also performed. KEY FINDINGS: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001). SIGNIFICANCE: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect.


Asunto(s)
Aminoácidos de Cadena Ramificada/uso terapéutico , Cardiotónicos/uso terapéutico , Daño por Reperfusión Miocárdica/prevención & control , Animales , Western Blotting , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/efectos de los fármacos , Ratas , Ratas Wistar , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo
11.
Life Sci ; 245: 117388, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32007576

RESUMEN

AIMS: The higher incidence rate of Alzheimer's disease (AD) among women has led to explorations on the association between estrogen deficiency and AD. Also, usage of antihypertensive drugs has been suggested to reduce the incidence of AD in elderly hypertensive patients. Thus, this study aimed to investigate the effects of telmisartan and/or 17ß-estradiol on a cognitively impaired ovariectomized rat model of AD. MAIN METHODS: 75 female Wistar rats were randomly allocated into five groups. One group was sham operated and the other four groups were subjected to ovariectomy, received D-galactose and either untreated or treated with telmisartan and/or 17ß-estradiol for 6 weeks. KEY FINDINGS: Ovariectomized rats showed cognitive impairment in Morris water maze and novel object recognition tests, increasing inflammatory biomarkers (tumor necrosis factor-α, and interleukin-1ß), increasing AD biomarkers (amyloid beta1-42, and acetylcholine esterase), and over activation of classical arm of renin angiotensin system (RAS) (ACE1/Ang2/AT1) in hippocampi. Also, hippocampi histopathological examination revealed amyloid beta deposition. Whereas, administration of telmisartan and/or 17ß-estradiol improved animals' behavior, alleviated histopathological alterations and reduced the level of inflammatory and AD biomarkers, modulated RAS activity favoring the novel neuroprotective arm (ACE2/Ang(1-7)/MasR). SIGNIFICANCE: Our findings suggest that combined administration of both drugs has synergetic neuroprotective effects; supporting their potential application in AD treatment.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Estradiol/uso terapéutico , Nootrópicos/uso terapéutico , Telmisartán/uso terapéutico , Enfermedad de Alzheimer/patología , Animales , Western Blotting , Disfunción Cognitiva/tratamiento farmacológico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Aprendizaje por Laberinto , Ovariectomía , Ratas , Ratas Wistar , Sistema Renina-Angiotensina/efectos de los fármacos
12.
Life Sci ; 245: 117385, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32014425

RESUMEN

AIM: The influence of thyroid hormones on exocrine pancreas function is poorly understood, and limited to the postnatal development period. Here, we evaluated the effects of hypo- and hyperthyroidism on the morphology and enzyme content of this tissue. MAIN METHODS: To induce hypothyroidism male Wistar rats were subjected to a thyroidectomy (Tx) or sham operated (SO). After 40 days, some of the Tx and SO rats were treated with T3 for 7 days. Following euthanization, the pancreas was removed and evaluated for morphology, as well as amylase, lipase and trypsin content, using histological and immunoreactive techniques analyses, respectively. Serum amylase levels were also evaluated. KEY FINDINGS: The pancreatic acinar cells of Tx rats were smaller, exhibited reduced Haematoxyllin stained areas, and contained lower amylase and lipase levels, indicative of low cell activity. Tx rats also presented higher collagen levels, and high trypsin content in pancreatic extracts. Interestingly, T3 administration reversed the observed acinar cell alterations and restored pancreatic enzyme content, by augmenting amylase and lipase and attenuating trypsin levels, but failed to change collagen content. Increased levels of lipase and decreased trypsin were also observed in T3-treated SO rats. SIGNIFICANCE: Thyroid hormones play an important role in acinar cell morphology and function. In the hypothyroid state there is a decrease in pancreatic enzyme levels that is restored with T3 treatment. In addition to participating in insulin sensitivity and glycemic control, THs also modulate enzyme expression and activity in the exocrine pancreas, consequently, delivering metabolic substrates to specific organs and tissues.


Asunto(s)
Páncreas Exocrino/patología , Hormonas Tiroideas/fisiología , Amilasas/sangre , Animales , Western Blotting , Hipertiroidismo/complicaciones , Hipertiroidismo/patología , Hipotiroidismo/complicaciones , Hipotiroidismo/patología , Masculino , Páncreas Exocrino/efectos de los fármacos , Páncreas Exocrino/fisiopatología , Ratas , Ratas Wistar , Tiroidectomía , Tirotropina/sangre , Triyodotironina/farmacología
13.
Life Sci ; 245: 117393, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32017872

RESUMEN

AIMS: Receptor for advanced glycation end products (RAGE) production is induced by diabetes. Microglial cells are activated by RAGE and produce inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and oxidative stress markers. Persistent production of TNF-α can provide a link between diabetes and Alzheimer's disease (AD). The purpose of this study was to investigate the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements on microglial cell activation and inflammatory conditions in the hippocampus of type 2 diabetic rats. MAIN METHODS: Diabetic and normal Wistar rats were divided into six groups. Oxidative stress markers (total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA)), mRNA expression and protein levels of RAGE and TNF-α were evaluated in the hippocampus of the controls and supplemented with ferrous sulfate and ω-3 PUFAs alone and together rats. Also, the entry of microglia cells into the hippocampus was evaluated by immunohistochemistry technique. KEY FINDINGS: Levels of the microglial activation (2.4 fold, p < 0.0001), MDA (84%, p < 0.0001) and oxidative stress index (OSI) (11%, p = 0.0094), mRNA expression and protein contents of RAGE (1.83 fold and 82% respectively) and TNF-α (2.25 fold and 86% respectively) were strongly influenced by negative effect of iron compared to the group receiving only ω-3 PUFAs which was dramatically improved by vitamin E. SIGNIFICANCE: These observations indicated that the co-supplementation of ferrous sulfate with ω-3 PUFAs decreases the anti-inflammatory ability of ω-3 PUFAs in the hippocampus of diabetic rats via RAGE/TNF-α-induced oxidative stress pathway up-regulation.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Ácidos Grasos Omega-3/farmacología , Compuestos Ferrosos/farmacología , Hipocampo/efectos de los fármacos , Animales , Hipocampo/química , Inflamación/tratamiento farmacológico , Malondialdehído/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
14.
Life Sci ; 246: 117420, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32050085

RESUMEN

PURPOSE: We intend to assess the effect of the conditioned medium of Caffeine pulsed MSCS in the amelioration of rheumatoid arthritis (RA)-afflicted rats. METHODS: MSCs were incubated with 0, 0.1, 0.5 or 1 mM Caffeine for 2 weeks. RA was induced by the injection of complete Freund's adjuvant (CFA) into the base of the tail of Wistar rats. According to in vitro studies, RA rats were intraperitoneally treated with MSCs, Caffeine (0.5 mM) pulsed MSCs or vehicle on day 14 when all rats had shown signs of RA. RESULTS: Our results suggest that the least effective dose concentration of Caffeine that can induce potent anti-inflammatory property in the MSC population is 0.5 mM. Without any significant impact on the vitality or MScs' marker, Caffeine at this concentration could induce lower levels of IFN-γ, IL-6, and IL-1ß and a higher level of IDO, TGF-ß, and IL-10 compared to other groups. Therefore, MSCs pulsed with Caffeine at 0.5 mM concentration was selected for in vitro studies. Caffeine pulsed MSCs could reduce the severity of the disease and improve weight-gaining more profoundly than treatment with MSCs alone. Furthermore, Caffeine pulsed MSCs caused a significant reduction in the serum levels C-reactive protein, Nitric oxide, Myeloperoxidase, TNF-α and conversely led a significant increase in the levels of IL-10 more prominent than the similar findings brought about by MSCs alone. CONCLUSION: In general, caffeine-treated MSCs may be a promising strategy for cell-based therapy of RA.


Asunto(s)
Artritis Reumatoide/terapia , Cafeína/farmacología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Artritis Experimental/inmunología , Artritis Experimental/terapia , Artritis Reumatoide/inmunología , Relación Dosis-Respuesta a Droga , Inmunomodulación , Masculino , Ratas , Ratas Wistar
15.
Life Sci ; 246: 117432, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32061867

RESUMEN

Our previous studies have shown that prenatal cold stress leads to placental inflammatory response and induces anxiety-like behavior reduced in offspring rats. However, the role and mechanisms by which prenatal cold stress affects offspring remain unclear. The aim of this study was to determine the metabolic profiles from the maternal serum and helpful in understanding the role and mechanisms by which prenatal cold stress affects the offspring. In this study, liquid chromatography-mass spectrometry (LC/MS) was used to analyze serum metabolites, and PCA, PLS-DA, and OPLS-DA were performed to analyze changes in metabolites in the maternal serum after cold stress of 3 or 7 days. The results showed that 19 metabolites in the CS (cold stress 7 days)-NS (control) group and 23 metabolites in the CT (cold stress 3 days)-NT (control) group were significantly altered. These metabolites were mainly associated with unsaturated fatty acid synthesis, and arachidonic acid, linoleic acid, and glutamine and glutamate metabolism. The data indicated that prenatal cold stress not only affected the maternal neuroendocrine system, but also affected the immune system, and lipid and amino acid metabolism. These results further supported the findings of our previous studies on the effects of prenatal cold stress on the mother and offspring. A more comprehensive understanding of these data may lead to maternal intervention that can reverse the damage of prenatal stressors.


Asunto(s)
Respuesta al Choque por Frío , Metabolómica , Efectos Tardíos de la Exposición Prenatal/etiología , Animales , Femenino , Cromatografía de Gases y Espectrometría de Masas , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Ratas Wistar
16.
Exp Parasitol ; 210: 107850, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32027893

RESUMEN

Experimental rats are important animal models, and a history of pathogenic infections in these animals will directly affect the animal trial results. Enterocytozoon bieneusi is a ubiquitous potential pathogen transmitted via the fecal-oral route. To determine the prevalence and genotypic distributions of E. bieneusi in experimental rats in China, 291 fresh fecal samples were collected from four medical experimental animal centers. Enterocytozoon bieneusi was screened via nested-PCR amplification of the internal transcribed spacer (ITS) region. Of the rats tested, 4.8% (14/291) were positive for E. bieneusi. Five E. bieneusi ITS genotypes (four known: EbpA, EbpC, CHY1, and N; one novel: SHR1) were detected among 14 sequenced samples. The dominant E. bieneusi genotype was EbpA (50.0%, 7/14). In the phylogenetic analysis, genotypes EbpA and EbpC belonged to the previously described group 1, genotypes N and SHR1 belonged to group 2, and genotype CHY1 belonged to the novel group 12. To our knowledge, this is the first report of E. bieneusi in experimental laboratory rats in China. Infections with this pathogen must be monitored in laboratory animals, and quality control officers in the medical experimental centers should attempt to trace the pathogen's source and stop its transmission.


Asunto(s)
Enterocytozoon/aislamiento & purificación , Microsporidiosis/microbiología , Animales , China/epidemiología , ADN de Hongos/aislamiento & purificación , Enterocytozoon/clasificación , Enterocytozoon/genética , Heces/microbiología , Femenino , Genotipo , Técnicas de Genotipaje , Microsporidiosis/epidemiología , Filogenia , Reacción en Cadena de la Polimerasa , Ratas , Ratas Endogámicas SHR , Ratas Sprague-Dawley , Ratas Wistar
17.
Zhongguo Zhen Jiu ; 40(2): 185-91, 2020 Feb 12.
Artículo en Chino | MEDLINE | ID: mdl-32100506

RESUMEN

OBJECTIVE: To explore the effect of electroacupuncture (EA) on insulin sensitivity, adipose tissue inflammatory reaction and silent information regulation factor 1(SIRT1)/nuclear factor kappa B (NF-κB) signaling pathway in obese rats. METHODS: A total of 100 SPF-grade Wistar male rats were collected. Thirteen rats of them were selected randomly as the normal group and fed with common forage, and the rest rats were fed with high-fat forage. Eight weeks later, 39 rats that met the obesity criteria were randomized into a model group, an EA group and a sham-EA group, 13 rats in each one. In each group, 3 rats were collected randomly and the hyperinsulinemic-euglycemic clamp was exerted to record glucose infusion rate (GIR) so as to determine insulin sensitivity. Afterwards, in the EA group, EA was applied to "Zusanli" (ST 36), "Fenglong" (ST 40), "Zhongwan" (CV 12) and "Guanyuan" (CV 4), stimulated with continuous wave, 2 Hz in frequency, 1 mA in current intensity, for 15 min. The treatment was given once every 2 days, 3 times a week, for 8 weeks totally. In the sham-EA group, the needles were inserted shallowly at the sites, 5 mm lateral to each of the acupoints stimulated in the EA group, and the electrodes were attached to the needle handles, but without electric stimulation exerted. The rest management was the same as the EA group. Before and after intervention, the body mass and the insulin sensitivity were measured. After intervention, the white adipose tissue was collected from the kidney in the rats. Western blot was adopted to detect the relative protein expressions of SIRT1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and acetylated NF-κB (Ac-NFκB). The real-time fluorescence quantitative PCR was used to detect the mRNA expressions of SIRT1, IL-6 and TNF-α. The immunofluorescence double labeling method was applied to detect the co-expression of SIRT1 and Ac-NFκB in adipose tissue. RESULTS: After fed with high-fat forage for 8 weeks, the body mass was significantly increased and GIR decreased in the rats of the model group as compared with the normal group (P<0.01), suggesting that the model of obese rat with insulin resistance was successfully established. After 8-week intervention, compared with the model group, the body mass was reduced and GIR increased in the rats of the EA group (P<0.01). The differences were not significant statistically in comparison between the sham-EA group and the model group (P>0.05). Compared with the normal group, in the model group, the protein and mRNA expressions of SIRT1 in adipose tissue were decreased, and the protein expression of Ac-NFκB increased, the protein and mRNA expressions of IL-6 and TNF-α increased (P<0.05, P<0.01). Compared with the model group, in the EA group, the protein and mRNA expressions of SIRT1 in adipose tissue were increased significantly, the protein expression of Ac-NFκB decreased, and the protein and mRNA expressions of IL-6 and TNF-α significantly decreased (P<0.05, P<0.01). There was no significant difference in each index between the sham-EA group and the model group (P>0.05). The results of immunofluorescence double labeling showed that SIRT1 and Ac-NFκB were co-expressed in adipose tissue. CONCLUSION: Electroacupuncture significantly reduces the body mass, inflammatory reaction conditions of adipose tissue and improves insulin sensitivity in obese rats. Regarding the potential mechanism, after the activation of SIRT1/NF-κB signaling pathway by electroacupuncture, and down-regulates the transcription of downstream inflammatory factors.


Asunto(s)
Tejido Adiposo/metabolismo , Electroacupuntura , FN-kappa B/metabolismo , Obesidad/patología , Transducción de Señal , Sirtuina 1/metabolismo , Puntos de Acupuntura , Animales , Interleucina-6/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo
18.
West Afr J Med ; 37(1): 7-12, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32030705

RESUMEN

BACKGROUND: Ketogenic diets (KD) have been used globally in epilepsy management. Similarly, supplementation of diets with magnesium has been associated with disease prevention and improvement. However, the effect of magnesium (Mg) supplementation in conjunction with KD on epilepsy has not yet been investigated. We hypothesized that magnesium supplementation in KD would improve the effectiveness of the diet. METHODS: Forty-eight male Wistar rats were used for the study. The animals were fed on 4 diet types: I-normal rat chow (ND), II-ND with Mg supplement (ND+Mg), III-medium chain ketogenic diet (KD) and IV-KD with Mg supplement (KD+Mg). Animals in each group were divided into 3: experimental, control and observatory. The experimental drug was intraperitoneal Pentylenetetrazole (PTZ) administered at 25 mg/kg. The rats were observed for 2 hours after the drug administration and induced seizures noted. The levels of serum electrolytes and plasma lipid levels were determined using standard methods. RESULTS: The seizure latency was significantly prolonged 60.8±0.5mins in group III compared with 8.7±2.1mins in group I (p<0.05). The seizure duration was 42.5±2.5mins in group III and 142.3±4.7 in group I (p<0.05). With Mg supplementation, seizure latency was 62.6±1.5mins in group IV and 7.9±0.7mins in group I (p<0.05). The seizure duration was 45.5±4.5min in group IV and 139.3±3.9mins in group II (p< 0.05). The KD-fed rats showed a tendency to develop dyslipidemia as evidenced by elevated Total Cholesterol /HDL and LDL/HDL (2.32±0.32 and 1.19±0.08) in group III, which was reversed in the KD+Mg fed group IV (1.96±0.32 and 1.08±0.09) with p<0.05. CONCLUSION: Mg supplementation of KD did not affect its antiseizure property and does not confer antiseizure effect on ND. Mg supplement showed a tendency to reduce derangement in lipid metabolism associated with KD.


Asunto(s)
Dieta Cetogénica , Metabolismo de los Lípidos/efectos de los fármacos , Magnesio/farmacología , Convulsiones/dietoterapia , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Humanos , Lípidos/sangre , Magnesio/administración & dosificación , Masculino , Pentilenotetrazol , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Convulsiones/sangre , Convulsiones/inducido químicamente
19.
Chem Biol Interact ; 317: 108966, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32004531

RESUMEN

Titanium dioxide nanoparticles (TiO2-NPs) are widely used in the food industry, cosmetics, personal care and paints among others. Through occupational exposure and daily consumption, and because of their small size, TiO2-NPs can enter the body through different routes such as oral, dermal and inhalation, and accumulate in multiple organs including the brain. TiO2-NPs cause severe damage to many cell types, however their effects in the central nervous system remain largely unexplored. Therefore, in the present study we determined the cytotoxic effect of TiO2-NPs on rat astrocytes. We tested the oxidant properties of TiO2-NPs through DTT depletion, and measured oxidative stress-induced damage in mitochondria, through oxidation of 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) and loss of mitochondrial membrane potential (ΔΨm) with Mitotracker Green FM. We further examined oxidative stress-derived responses such as IκB-α degradation by Western Blot, NF-κB translocation by EMSA, autophagy induction by LC3-II levels, and expression of the inflammasome protein NLRP3. TiO2-NPs showed high oxidant properties and induced strong oxidative stress in astrocytes following their internalization, causing mitochondrial damage detected by ΔΨm loss. Responses against oxidative damage such as NF-κB translocation and autophagy were induced and NLRP3 protein expression was downregulated, indicating lower inflammasome-mediated responses in astrocytes. These results support TiO2-NPs cytotoxicity in astrocytes, cells that play key roles in neuronal homeostasis and their dysfunction can lead to neurological disorders including cognitive impairment and memory loss.


Asunto(s)
Astrocitos/efectos de los fármacos , Autofagia/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Animales Recién Nacidos , Astrocitos/metabolismo , Células Cultivadas , Regulación hacia Abajo , Nanopartículas del Metal , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ratas , Ratas Wistar , Titanio
20.
Artículo en Chino | MEDLINE | ID: mdl-32062887

RESUMEN

Objective: To investigate the antagonistic effect of diallyl sulfide (DAS) against peripheral nerve injury induced by n-hexane in rats. Methods: A total of 68 adult male Wistar rats were selected, among which 50 were randomly selected and divided into blank control group, DAS control group (100 mg/kg·bw) , n-hexane model group, low-dose DAS intervention group (50 mg/kg·bw) , and high-dose DAS intervention group (100 mg/kg·bw) . A rat model of peripheral nerve injury was established by n-hexane exposure, and the rats were treated with DAS at different doses. The changes in pyrrole adducts and behavior were observed, a metabolic analysis was performed for serum pyrrole adducts, and the intervention effect was evaluated. The remaining 18 rats were randomly assigned to the n-hexane model group, the low-dose DAS intervention group, and the high-dose DAS intervention group, with 6 rats in each group, as satellite groups used for the toxicokinetic analysis of serum pyrrole adducts. Results: Compared with the blank control group, the n-hexane model group and low-and high-dose DAS intervention groups had a significant reduction in body weight since week 2 (P<0.01) . Compared with the n-hexane model group at the end of the experiment at week 7, the high-dose DAS intervention group had a significantly higher body weight (P<0.05) , while there was no significant difference in body weight between the n-hexane model group and the low-dose DAS intervention group (P>0.05) . The n-hexane model group developed gait abnormality at week 2 of poisoning, while the low-and high-dose DAS intervention groups developed gait abnormality at weeks 3 and 5 of poisoning, respectively. At the end of the experiment, the n-hexane model group and the low-and high-dose DAS intervention groups had a significantly higher gait score than the blank control group (P<0.01) . At the end of the experiment, the n-hexane model group and the low-dose DAS intervention group had significantly shorter latency in rotarod test than the blank control group (P<0.01) , while there was no significant difference in latency between the DAS control group and the high-dose DAS intervention group (P>0.05) . Compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in latency in rotarod test (P<0.01) . Compared with blank control group, the n-hexane model group and the low-dose DAS intervention group had a significant increase in mean nerve conduction velocity (P<0.01) , while there was no significant difference between the blank control group and the DAS control group or high-dose DAS intervention group (P>0.05) , and compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in nerve conduction velocity (P<0.01) . Compared with the blank control group at the end of the experiment at week 7, the n-hexane model group and the low-and high-dose DAS intervention groups had significant increases in the concentration of pyrrole adducts in serum, urine, and hair (P<0.01) , while there was no significant difference between the blank control group and the DAS control group (P>0.05) , and the high-dose DAS intervention group had a significantly lower concentration of pyrrole adducts in serum, urine, and hair than the low-dose DAS intervention group (P<0.05) . Serum pyrrole adducts reached the peak level at 9-12 hours and then started to decrease. Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significantly shorter half-life period of serum pyrrole adducts (P<0.01) . Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significant reduction in the area under the curve of serum pyrrole adducts (P<0.05) . Conclusion: DAS can antagonize peripheral nerve injury induced by n-hexane.


Asunto(s)
Compuestos Alílicos/farmacología , Hexanos/toxicidad , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Sulfuros/farmacología , Animales , Masculino , Traumatismos de los Nervios Periféricos/inducido químicamente , Ratas , Ratas Wistar
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