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1.
Biomed Environ Sci ; 34(5): 356-363, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34059172

RESUMO

Objective: This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. Methods: In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. Results: Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine ß-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. Conclusion: DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.


Assuntos
Dieta , Suplementos Nutricionais , Deficiência de Ácido Fólico/metabolismo , Homocisteína/metabolismo , Sarcosina/análogos & derivados , Animais , Biomarcadores/metabolismo , Cromatografia Líquida , Fígado/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Sarcosina/administração & dosagem , Sarcosina/metabolismo
2.
Int J Mol Sci ; 22(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064311

RESUMO

Dephosphorylation of target proteins at serine/threonine residues is one of the most crucial mechanisms regulating their activity and, consequently, the cellular functions. The role of phosphatases in synaptic plasticity, especially in long-term depression or depotentiation, has been reported. We studied serine/threonine phosphatase activity during the protein synthesis blocker (PSB)-induced impairment of long-term potentiation (LTP). Established protein phosphatase 2B (PP2B, calcineurin) inhibitor cyclosporin A prevented the LTP early phase (E-LTP) decline produced by pretreatment of hippocampal slices with cycloheximide or anisomycin. For the first time, we directly measured serine/threonine phosphatase activity during E-LTP, and its significant increase in PSB-treated slices was demonstrated. Nitric oxide (NO) donor SNAP also heightened phosphatase activity in the same manner as PSB, and simultaneous application of anisomycin + SNAP had no synergistic effect. Direct measurement of the NO production in hippocampal slices by the NO-specific fluorescent probe DAF-FM revealed that PSBs strongly stimulate the NO concentration in all studied brain areas: CA1, CA3, and dentate gyrus (DG). Cyclosporin A fully abolished the PSB-induced NO production in the hippocampus, suggesting a close relationship between nNOS and PP2B activity. Surprisingly, cyclosporin A alone impaired short-term plasticity in CA1 by decreasing paired-pulse facilitation, which suggests bi-directionality of the influences of PP2B in the hippocampus. In conclusion, we proposed a minimal model of signaling events that occur during LTP induction in normal conditions and the PSB-treated slices.


Assuntos
Região CA1 Hipocampal/metabolismo , Região CA3 Hipocampal/metabolismo , Calcineurina/genética , Potenciação de Longa Duração/genética , Potenciais Sinápticos/genética , Animais , Anisomicina/farmacologia , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA3 Hipocampal/citologia , Região CA3 Hipocampal/efeitos dos fármacos , Calcineurina/metabolismo , Inibidores de Calcineurina/farmacologia , Cicloeximida/farmacologia , Ciclosporina/farmacologia , Giro Denteado/citologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Regulação da Expressão Gênica , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Microtomia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/genética , Óxido Nítrico/química , Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Wistar , S-Nitroso-N-Acetilpenicilamina/química , S-Nitroso-N-Acetilpenicilamina/farmacologia , Potenciais Sinápticos/efeitos dos fármacos , Técnicas de Cultura de Tecidos
3.
Arch Oral Biol ; 128: 105170, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34082374

RESUMO

OBJECTIVE: The aim of this study was to quantify the temporal changes in inflammation and TRPA1, TRPV1 and CGRP expression in the trigeminal ganglion during force-induced orthodontic pain. DESIGN: Orthodontic force was applied to both maxillary first molars in 8-week-old Wistar rats for 12 h, 24 h, 3 d or 7 d. The rat grimace scale (RGS) score and duration of face grooming were used to measure orthodontic pain. Western blotting was performed to assess TRPA1, TRPV1 and CGRP expression in trigeminal ganglia. NF-кB levels and colocalization of TRPA1, TRPV1 and CGRP were evaluated by immunofluorescent staining. RESULTS: Application of continuous force significantly increased pain behaviours at 1 and 3 d. NF-кB significantly increased in periodontal ligament at 12 h until 3 d. TRPV1 was significantly elevated within 1 d; TRPA1 significantly increased from 1-3 d; CGRP expression significantly increased from 12 h to 3 d. The TRPV1/TRPA1 expression ratio was highest at 12 h; the TRPA1/TRPV1 ratio peaked at 3 d. The percentages of trigeminal neurons co-expressing TRPA1/TRPV1, TRPA1/CGRP, and TRPV1/CGRP significantly increased by 12 h and peaked at 24 h. CGRP expression had a stronger positive correlation with TRPV1 than TRPA1. CONCLUSIONS: Inflammation induced by application of orthodontic force sensitizes trigeminal TRPV1 and TRPA1; TRPV1 is primarily activated as an early response, whereas TRPA1 is activated as a late response. Activation of both nociceptors results in CGRP release. Thus, blocking both TRPV1 and TRPA1 may represent a primary therapeutic target for relief of orthodontic pain.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Canais de Cátion TRPV , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dor , Ratos , Ratos Wistar , Canal de Cátion TRPA1 , Gânglio Trigeminal/metabolismo
4.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(4. Vyp. 2): 6-13, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34078853

RESUMO

OBJECTIVE: To develop of a chronic sleep restriction model in rats by repeated sleep deprivation using an orbital shaker and to determine whether this model leads to disturbances in sleep homeostatic mechanisms. MATERIAL AND METHODS: Male Wistar rats (7-8 months old) underwent sleep restriction for five consecutive days: 3 h of sleep deprivation and 1 h of sleep opportunity repeating throughout each day. Polysomnograms were recorded telemetrically throughout the day before sleep restriction (baseline), on the 1st, 3rd, 5th day of sleep restriction and 2 days after the end of sleep restriction (recovery period). RESULTS: During the period of sleep restriction, the total amount of slow-wave sleep (SWS) and rapid eye movement (REM) sleep decreased by 61% and 55%, respectively, compared to baseline. On the first day of recovery, amount of SWS increased mainly in the dark (active) phase of the day, while REM sleep increased in both light and dark phases; there was no marked rebound of daily SWS amount, while REM sleep increased by 30% from baseline. On the first day of recovery, an elevation of EEG beta and sigma power in sleep states was observed mainly in the light phase of the day. The loss of deep SWS throughout the sleep restriction period increased from 50% on 1st day to 75% on 5th day. The level of deep SWS remained below the baseline by 15-20% on the two subsequent days of recovery. The findings suggest that homeostatic mechanisms of SWS are persistently impaired after 5-day chronic sleep restriction. Besides, a decline of wakefulness accompanied by an increase of SWS in the active phase of the recovery period indicates a disruption in circadian rhythm. CONCLUSION: The proposed model leads to the disruption of sleep homeostatic mechanisms, which, in turn, impede compensation of SWS loss caused by chronic insufficient sleep.


Assuntos
Eletroencefalografia , Sono , Animais , Masculino , Ratos , Ratos Wistar , Privação do Sono , Sono REM , Vigília
5.
Acta Cir Bras ; 36(4): e360408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076065

RESUMO

PURPOSE: To explore the role and molecular mechanisms of neuroprotective effects of octreotide in alcohol-induced neuropathic pain. METHODS: Male Wistar rats were employed and were administered a chronic ethanol diet containing 5% v/v alcohol for 28 days. The development of neuropathic pain was assessed using von Frey hair (mechanical allodynia), pinprick (mechanical hyperalgesia) and cold acetone drop tests (cold allodynia). The antinociceptive effects of octreotide (20 and 40 µg·kg-1) were assessed by its administration for 28 days in ethanol-treated rats. ANA-12 (0.25 and 0.50 mg·kg-1), brain-derived neurotrophic factor (BDNF) receptor blocker, was coadministered with octreotide. The sciatic nerve was isolated to assess the biochemical changes including hydrogen sulfide (H2S), cystathionine ß synthase (CBS), cystathionine γ lyase (CSE), tumor necrosis factor-α (TNF-α), BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2). RESULTS: Octreotide significantly attenuated chronic ethanol-induced neuropathic pain and it also restored the levels of H2S, CBS, CSE, BDNF, Nrf2 and decreased TNF-α levels. ANA-12 abolished the effects of octreotide on pain, TNF-α, BDNF, Nrf2 without any significant effects on H2S, CBS, CSE. CONCLUSIONS: Octreotide may attenuate the behavioral manifestations of alcoholic neuropathic pain, which may be due to an increase in H2S, CBS, CSE, BDNF, Nrf2 and a decrease in neuroinflammation.


Assuntos
Analgésicos/farmacologia , Neuralgia , Octreotida/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo , Cistationina beta-Sintase , Cistationina gama-Liase , Etanol , Sulfeto de Hidrogênio , Hiperalgesia , Masculino , Fator 2 Relacionado a NF-E2 , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(5): 535-540, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34112288

RESUMO

OBJECTIVE: To explore whether resveratrol (RSV) could activate silent information regulator 1 (SIRT1) to regulate the activation of NOD-like receptor protein 3 (NLRP3) inflammasome in sepsis induced intestinal injury model, and then reduce intestinal inflammation and cell apoptosis, so as to play a protective role in intestinal barrier function. METHODS: (1) In vitro experiment: human Colorectal adenocarcinoma cells (Caco-2) were cultured, which were divided into normal group (normal culture on complete medium for 48 hours), lipopolysaccharide (LPS) group (normal culture on complete medium for 24 hours, then LPS containing 2 mg/L complete medium intervention for 6 hours), RSV low, medium and high concentration groups and SIRT1 inhibitor (EX-527) group (complete medium normal culture for 24 hours, LPS containing 2 mg/L complete medium intervention for 6 hours, followed by RSV 10, 20, 40 µmol/L or EX-527 10 µmol/L intervention for 6 hours, respectively). The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-18, IL-1ß) in the cell supernatant were determined by enzyme linked immunosorbent assay (ELISA). The apoptosis level of the cells was detected by flow cytometry. Western blotting was used to detect the protein levels of NLRP3, SIRT1, caspase-1 and apoptosis-related point-like protein (ASC). (2) In vivo experiment: according to random number table method, 24 male Wistar rats were divided into sham operation group (Sham group), cecal ligation and perforation (CLP) 6 hours group (CLP 6 h group), CLP 24 h group and RSV intervention group [RSV (20 mg/kg) was intraperitoneally injected 6 hours and 12 hours after CLP], with 6 rats in each group. The levels of NLRP3, caspase-1 and ASC in the intestine of rats were detected by immunohistochemistry. RESULTS: (1) Compared with the normal group, the levels of inflammatory factors in the cell supernatant of the LPS group were increased and the expression of SIRT1 protein was decreased, while the protein expressions of NLRP3, caspase-1 and ASC were increased. Compared with LPS group, different concentrations of RSV reduced the level of inflammatory factors, increased the activity of SIRT1, inhibited the expression of NLRP3 inflammasome and its downstream products caspase-1 and ASC, and the effect of high concentration of RSV (40 µmol/L) was the most significant [TNF-α (ng/L): 8.77±0.43 vs. 12.66±0.81, IL-6 (ng/L): 1.35±0.20 vs. 1.93±0.09, IL-1ß (ng/L): 1.05±0.04 vs. 1.31±0.07, IL-18 (ng/L): 519.50±11.16 vs. 622.70±30.69, SIRT1/ß-actin: 0.80±0.05 vs. 0.58±0.02, caspase-1/ß-actin: 0.55±0.06 vs. 0.78±0.06, ASC/ß-actin: 0.78±0.08 vs. 1.04±0.15, all P < 0.05], while SIRT1 inhibitor EX-527 had the opposite effects. There was no significant difference in the apoptosis rate among normal group, LPS group, and low, medium and high concentration RSV groups, as well as EX-527 group [(7.03±0.57)%, (9.67±0.55)%, (9.57±0.70)%, (9.30±2.15)%, (9.87±0.97)%, (9.07±0.93)%, F = 2.590, P = 0.082]. (2) Immunohistochemical results showed that compared with the Sham group, the expressions of NLRP3 inflammasomes and downstream products caspase-1 and ASC in the intestinal epithelial cells in CLP 6 h group, CLP 24 h group and RSV intervention group were significantly increased. The percentage of ASC-positive area in intestinal epithelium of RSV intervention group was significantly lower than that of CLP 6 h group [(15.22±2.73)% vs. (19.88±2.67)%, P < 0.05], and the expressions of NLRP3 and caspase-1 were significantly lower than those of CLP 24 h group [(9.31±1.37)% vs. (13.19±1.92)%, (19.57±3.92)% vs. (27.28±6.33)%, both P < 0.05]. CONCLUSIONS: After sepsis, high concentration of RSV could inhibit the activation of NLRP3 inflammasome by activating SIRT1, thereby reduce the expression of caspase-1 and ASC, and inhibit the secretion of inflammatory factors to reduce the inflammatory response.


Assuntos
Proteínas NLR , Sepse , Sirtuína 1 , Animais , Células CACO-2 , Humanos , Interleucinas , Mucosa Intestinal , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ratos Wistar , Resveratrol/farmacologia , Sepse/tratamento farmacológico , Fator de Necrose Tumoral alfa
7.
Zhen Ci Yan Jiu ; 46(5): 368-74, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085458

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on left-cardiac function, contents of serum TNF-α and IL-6 and expression of myocardial farnesoid X receptor(FXR), small heterodimer partner (SHP), apoptosis inducing factor (AIF) and heat shock proteins 70 (HSP70) genes in myocardial ischemia-reperfusion injury (MIRI) rats, so as to explore its mechanisms underlying improvement of ischemic myocardial injury. METHODS: Forty male Wistar rats were randomly divided into normal control, sham operation, MIRI model and EA pretreatment groups, with 10 rats in each group. Rats of the sham operation group received exposure of the thorax and heart. The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery (LAD). EA (2 Hz/100 Hz and 1 mA) was applied to bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, once a day for 7 days. The left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP)and maximal rates of rise and fall of left ventricular pressure (±dp/dtmax) were detected, the contents of serum TNF-α and IL-6 were detected by using enzyme-linked immunosorbent assay (ELISA), and the expression of FXR, SHP, AIF and HSP70 apoptotic genes in the myocardial tissue were measured by fluorescent quantitative RT-PCR. RESULTS: Compared with the normal control group, the LVEDP, contents of serum TNF-α and IL-6, and the expression levels of myocardial FXR, SHP, AIF and HSP70 mRNAs were significantly increased (P<0.05), while LVSP and ±dp/dtmax levels were obviously decreased in the model group (P<0.05). In comparison with the model group, MIRI-induced increases of LVEDP, TNF-α and IL-6 contents, and FXR, SHP and AIF mRNA expression and decreases of ±dp/dtmax and LVSP levels were reversed(P<0.05), except HSP70 mRNA expression with significantly increased (P<0.05) in the EA pretreatment group. CONCLUSION: EA pretreatment can protect the left ventricular function of the ischemic heart in MIRI rats, which may be related to its effects in reliving peripheral inflammation and regulating the expression levels of apoptosis-related factors FXR, SHP, AIF and HSP70 in the myocardium.


Assuntos
Eletroacupuntura , Traumatismo por Reperfusão Miocárdica , Pontos de Acupuntura , Animais , Apoptose/genética , Masculino , Células Musculares , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/terapia , Ratos , Ratos Wistar
8.
Zhen Ci Yan Jiu ; 46(5): 375-9, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085459

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) and "Huiyang" (BL35) on the expression of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and cellular oncogene fos (c-fos) phosphorylated of spinal dorsal horn in rats with interstitial cystitis (IC). METHODS: Eighteen female Wistar rats were randomly divided into control, model and EA groups, with 6 rats in each group. The IC model was established by intraperitoneal injection of cyclophosphamide (150 mg/kg). EA (30 Hz, 1 mA) was applied to bilateral BL32 and BL35 for 20 min, once daily for 3 consecutive days. The bladder pain was measured by using a Von Frey at 48 h after modeling and 24 h after EA. The expression levels of p-ERK1/2 and c-fos protein in L6-S1 segment of spinal cord were detected by Western blot, and the expression of p-ERK1/2 and c-fos in the right spinal dorsal horn were displayed by immunofluorescence staining. RESULTS: After modeling, the bladder mechanical pain threshold (PT) was significantly decreased (P<0.05), the protein expression of p-ERK1/2 and c-fos in the spinal cord was increased (P<0.05) and the immunofluorescence surface density of p-ERK1/2 and c-fos in the right dorsal horn of spinal cord was increased (P<0.05) in the model group relevant to the control group. After EA intervention, IC-induced reduction of PT, and increases of the expression of p-ERK1/2 and c-fos as well as immunofluorescence surface density of p-ERK1/2 and c-fos were reversed in the EA group relevant to the model group (P<0.05). CONCLUSION: EA at BL 32 and BL 35 has an analgesic effect in IC rats, which may be related to its effect in down-regulating the expression of p-ERK1/2 and c-fos in spinal dorsal horn.


Assuntos
Cistite Intersticial , Eletroacupuntura , Animais , Feminino , Sistema de Sinalização das MAP Quinases , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo
9.
Int J Nanomedicine ; 16: 3173-3183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007172

RESUMO

Aim: Cerebral ischemic injury is one of the debilitating diseases showing that inflammation plays an important role in worsening ischemic damage. Therefore, studying the effects of some potential anti-inflammatory compounds can be very important in the treatment of cerebral ischemic injury. Methods: This study investigated anti-inflammatory effects of triblock copolymer nanomicelles loaded with curcumin (abbreviated as NC) in the brain of rats following transient cerebral ischemia/reperfusion (I/R) injury in stroke. After preparation of NC, their protective effects against bilateral common carotid artery occlusion (BCCAO) were explored by different techniques. Concentrations of free curcumin (C) and NC in liver, kidney, brain, and heart organs, as well as in plasma, were measured using a spectrofluorometer. Western blot analysis was then used to measure NF-κB-p65 protein expression levels. Also, ELISA assay was used to examine the level of cytokines IL-1ß, IL-6, and TNF-α. Lipid peroxidation levels were assessed using MDA assay and H&E staining was used for histopathological examination of the hippocampus tissue sections. Results: The results showed a higher level of NC compared to C in plasma and organs including the brain, heart, and kidneys. Significant upregulation of NF-κB, IL-1ß, IL-6, and TNF-α expressions compared to control was observed in rats after induction of I/R, which leads to an increase in inflammation. However, NC was able to downregulate significantly the level of these inflammatory cytokines compared to C. Also, the level of lipid peroxidation in pre-treated rats with 80mg/kg NC was significantly reduced. Conclusion: Our findings in the current study demonstrate a therapeutic effect of NC in an animal model of cerebral ischemia/reperfusion (I/R) injury in stroke through the downregulation of NF-κB-p65 protein and inflammatory cytokines.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Inflamação/tratamento farmacológico , Micelas , NF-kappa B/metabolismo , Nanopartículas/química , Polímeros/química , Transdução de Sinais , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Curcumina/farmacologia , Citocinas/sangue , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Inflamação/complicações , Inflamação/patologia , Lactatos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Nanopartículas/ultraestrutura , Fosforilação/efeitos dos fármacos , Polietilenoglicóis/química , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
10.
Braz J Med Biol Res ; 54(7): e10865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34008758

RESUMO

This study verified the effects of respiratory muscle training (RMT) on hemodynamics, heart rate (HR) variability, and muscle morphology in rats with streptozotocin-induced diabetes mellitus (DM). Thirty-six male Wistar rats were randomized into 4 groups and 34 completed the study: i) sham-sedentary (Sham-ST; n=9); ii) sham-RMT (Sham-RMT; n=9); iii) DM-sedentary (DM-ST; n=8); and iv) DM-RMT (DM-RMT; n=8). Hemodynamics were assessed by central cannulation, and R-R intervals were measured by electrocardiogram. In addition, the effects of RMT on the cross-sectional area of the diaphragm, anterior tibial, and soleus muscles were analyzed. The induction of DM by streptozotocin resulted in weight loss, hyperglycemia, reduced blood pressure, and attenuated left ventricular contraction and relaxation (P<0.05). We also observed a decrease in root mean square of successive differences between adjacent RR intervals (RMSSD) index and in the cross-sectional area of the muscles assessed, specifically the diaphragm, soleus, and anterior tibial muscles in diabetic rats (P<0.05). Interestingly, RMT led to an increase in RMSSD in rats with DM (P<0.05). The induction of DM produced profound deleterious changes in the diaphragmatic and peripheral muscles, as well as impairments in cardiovascular hemodynamics and autonomic control. Nevertheless, RMT may beneficially attenuate autonomic changes and improve parasympathetic modulation.


Assuntos
Diabetes Mellitus Experimental , Animais , Exercícios Respiratórios , Frequência Cardíaca , Hemodinâmica , Masculino , Ratos , Ratos Wistar , Músculos Respiratórios
11.
Immunopharmacol Immunotoxicol ; 43(3): 309-318, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34032546

RESUMO

BACKGROUND: Depression affects people feeling to be anxious, worried, and restless. They also lose interest in activities, concentrating and appetite, they finally may attempt suicide. Depression is the second chronic disease, as a source of the global burden of disease, after heart disease. Its prevalence elevated seven times during the COVID-19. AIM: The current study was designed to evaluate camphor neuroprotective role against rats' ciprofloxacin-induced depression. MATERIALS AND METHODS: Depression was induced by administration of ciprofloxacin (50 mg/kg; orally) for 21 days. Wister albino male rats were divided into five groups. Group I (normal control): rats were given normal saline. Group II: rats received camphor (10 mg/kg; i.p.) for 21 days. Group III (depression control): rats received ciprofloxacin only. Groups IV and V: rats received camphor (5 and 10 mg/kg; i.p.) for 21 days concurrent with ciprofloxacin. Behavior tests as forced swimming test, activity cage, and rotarod were estimated. Oxidative stress and antioxidant biomarkers as malondialdehyde (MDA), nitric oxide (NO), catalase, and nuclear factor erythroid 2-related factor 2 (Nrf-2) besides inflammatory biomarkers as Toll-like receptor 4 (TLR4) and tumor necrosis factor alpha (TNF-α) as well as neurotransmitters were determined. Finally, histopathological examination was done. RESULTS: Camphor increased catalase and Nrf-2 activities, decreased NO, MDA, TNF-α, TLR4 serum levels, and elevating brain contents of serotonin, dopamine, gamma-amino butyric acid (GABA) and P190-RHO GTP protein with normal neuronal cells of the frontal cortex. CONCLUSION: Camphor has neuroprotective effect via modulation of Nrf-2 and TLR4 against ciprofloxacin-induced depression in rats.


Assuntos
Cânfora/farmacologia , Ciprofloxacina/efeitos adversos , Depressão , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptor 4 Toll-Like/metabolismo , Animais , /metabolismo , Ciprofloxacina/farmacologia , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/metabolismo , Masculino , Ratos , Ratos Wistar , /metabolismo
12.
Clinics (Sao Paulo) ; 76: e2513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978073

RESUMO

OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.


Assuntos
Lesão Pulmonar Aguda , Melatonina , Traumatismo por Reperfusão , Acetilcisteína/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Isquemia , Melatonina/uso terapêutico , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/prevenção & controle
13.
Chin J Physiol ; 64(2): 106-114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33938821

RESUMO

Studies indicate that rapid weight gain at critical development stages, such as the lactation period, is associated with the development of obesity, cardiovascular diseases, and diabetes in the long term. In addition to metabolic changes during adulthood, overweight/obesity may influence reproductive function. Human and animal studies suggest that lifestyle changes through exercise and/or controlled diet result in improved semen quality in obese individuals. However, the relationship between exercise volume/intensity and reproductive capacity effects remains inconclusive. The present study aimed to evaluate the effects of moderate intensity endurance training and high-intensity interval training (HIIT) on the reproductive parameters of lactating overfed male Wistar rats. Postnatal overfeeding was induced by applying the litter size reduction method. Forty males Wistar rats were used, divided into four groups: one with control litters (CLs) (10 animals/litter-sedentary) and three with small litters (SLs) (4 animals/litter), divided into sedentary, moderate endurance training, and HIIT. Morphologic, metabolic, and reproductive variables were analyzed. SL sedentary group showed increased body weight, adiposity, and decreased relative weight of the seminal vesicle, prostate, and epididymis as well as changes in the insulin tolerance and oral glucose tolerance tests glycemic tests compared to CL sedentary group. Endurance and HIIT protocols were efficient in improving the glycemic metabolism, central fat accumulation of trained groups and did not affect reproductive parameters. Endurance and HIIT protocols proved to be effective in reversing these metabolic changes without impairing the evaluated reproductive parameters.


Assuntos
Treino Aeróbico , Treinamento Intervalado de Alta Intensidade , Adulto , Animais , Feminino , Humanos , Lactação , Masculino , Ratos , Ratos Wistar , Análise do Sêmen
14.
Arch Esp Urol ; 74(4): 427-434, 2021 May.
Artigo em Espanhol | MEDLINE | ID: mdl-33942731

RESUMO

OBJECTIVES: This study was aimed at assessing the ability of ischemia-modified albumin (IMA) to predict renal injury by associating biochemical, functional, and pathological findings with various degrees of ureteral obstruction. METHODS: Twenty-four rats were randomized into three groups, and their blood was sampled to determine the creatinine and IMA values and renal scintigraphy was done at the start and on postoperative day 7. In the sham group, the ureter was untouched; in the partial group, the ureter was gently embedded into the psoas muscle; and in the complete group, the ureter was compathologically, and all parameters were statistically evaluated. RESULTS: IMA was significantly associated with functional changes, creatinine values, and pathology scores (r = -0.729, r = 0.771, r = 0.827 respectively; p < 0.001). The postoperative IMA values of the partial and complete group were significantly higher than the respective preoperative values (p < 0.001, p < 0.001; p < 0.05, respectively). Additionally, the postoperative IMA values of the complete group were significantly higher than that of the sham and partial groups (p < 0.001, p = 0.001; p < 0.05, respectively). CONCLUSIONS: IMA, which is strongly associated with renal functional and pathological variations, appears to be a valuable parameter for predicting renal injury and may warn clinicians before the irreversible phases of obstructive uropathy occur. More extensive studies with human participants may prove advantageous.


Assuntos
Rim , Albumina Sérica , Animais , Biomarcadores , Ratos , Ratos Wistar , Albumina Sérica Humana
15.
Zhen Ci Yan Jiu ; 46(4): 295-300, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33931994

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA. METHODS: A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg-1·d-1), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1ß(IL-1ß) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively. RESULTS: Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score,the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1ß,IL-18 were significantly increased (P<0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1,IL-1ß,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group (P<0.01, P<0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased (P<0.05). CONCLUSION: EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.


Assuntos
Artrite Gotosa , Eletroacupuntura , Animais , Artrite Gotosa/genética , Artrite Gotosa/terapia , Catepsina B/genética , Inflamassomos/genética , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ratos , Ratos Wistar
16.
Nihon Yakurigaku Zasshi ; 156(3): 166-170, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33952846

RESUMO

In the brains of patients with Alzheimer's disease, a decrease in phosphatidylinositol phosphate (PIP) requiring Cl--ATPase activity was found. In cultured rat hippocampal neurons, pathophysiological concentrations of amyloid ß proteins (Aßs≤10 nM) lowered PIP levels and Cl--ATPase activity with an increase in intracellular Cl- concentrations, resulting in Cl--dependent enhancements in glutamate neurotoxicity and, ultimately, neuronal cell death. Pathophysiological concentrations of Aßs(0.1-10 nM) directly lowered phosphatidylinositol-4-kinase. Non-toxic peptide fragments of Aß, such as Ile-Gly-Leu, recovered Aß-induced inhibition of recombinant human phosphatidylinositol-4-kinase IIα (PI4KIIα) and the intrahippocampally administered Aß-induced degeneration of hippocampal neurons and impairment of spatial memory in mice. Agents with the potential to block these neurotoxic mechanisms of Aß were summarized herein as (1) Aß antagonists, (2) substrates of PI4K, (3) PI4K product, (4) PI4K activators, and (5) GABAc receptor stimulants.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Adenosina Trifosfatases/metabolismo , Doença de Alzheimer/tratamento farmacológico , Animais , Morte Celular , Células Cultivadas , Hipocampo/metabolismo , Humanos , Camundongos , Fragmentos de Peptídeos , Ratos , Ratos Wistar
17.
Oxid Med Cell Longev ; 2021: 7848027, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936386

RESUMO

Abnormal autophagy and oxidative stress contribute to angiotensin II- (Ang II-) induced cardiac hypertrophy and heart failure. We previously showed that Ang II increased Rap1GAP gene expression in cardiomyocytes associated with hypertrophy and autophagy disorders. Using real-time PCR and Western blot, we found that Rap1GAP expression was increased in the heart of Sprague Dawley (SD) rats infused by Ang II compared with saline infusion and in Ang II vs. vehicle-treated rat neonatal cardiomyocytes. Overexpression of Rap1GAP in cultured cardiomyocytes exacerbated Ang II-induced cardiomyocyte hypertrophy, reactive oxygen species (ROS) generation, and cell apoptosis and inhibited autophagy. The increased oxidative stress caused by Rap1GAP overexpression was inhibited by the treatment of autophagy agonists. Knockdown of Rap1GAP by siRNA markedly attenuated Ang II-induced cardiomyocyte hypertrophy and oxidative stress and enhanced autophagy. The AMPK/AKT/mTOR signaling pathway was inhibited by overexpression of Rap1GAP and activated by the knockdown of Rap1GAP. These results show that Rap1GAP-mediated pathway might be a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which could be a potential target for the future treatment of cardiac hypertrophy and heart failure.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Angiotensina II , Animais , Autofagia , Cardiomegalia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Ratos Wistar
18.
Oxid Med Cell Longev ; 2021: 8832863, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936388

RESUMO

Reactive oxygen species (ROS) production has been associated with neuronal death. ROS are also involved in mitochondrial fission, which is mediated by Dynamin-related protein 1 (Drp1). The regulation of mitochondrial fragmentation mediated by Drp1 and its relationship to mitochondrial ROS (mtROS) in neuronal death have not been completely clarified. The aim of this study is to evaluate the role of mtROS in cell death and their involvement in the activation of Drp1 and mitochondrial fission in a model of cell death of cultured cerebellar granule neurons (CGN). Neuronal death of CGN induced by potassium deprivation (K5) and staurosporine (ST) triggers mitochondrial ROS production and mitochondrial fragmentation. K5 condition evoked an increase of Drp1 phosphorylation at Ser616, but ST treatment led to a decrease of Drp1 phosphorylation. Moreover, the death of CGN induced by both K5 and ST was markedly reduced in the presence of MitoTEMPO; however, mitochondrial morphology was not recovered. Here, we show that the mitochondria are the initial source of ROS involved in the neuronal death of CGN and that mitochondrial fragmentation is a common event in cell death; however, this process is not mediated by Drp1 phosphorylation at Ser616.


Assuntos
Dinaminas/genética , Mitocôndrias/metabolismo , Neurônios/metabolismo , Animais , Morte Celular , Humanos , Fosforilação , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio
19.
Zhonghua Gan Zang Bing Za Zhi ; 29(4): 362-368, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33979964

RESUMO

Objective: To investigate the effect of natural hyperoxic environment on liver lipid metabolism and liver function based on the bile acid-farnesoid X receptor pathway in sub-healthy rats. Methods: Forty adult male Wistar rats were randomly divided into control group (n = 10) and sub-healthy model group (n = 30). The control group was fed a normal diet, and the model group was fed a high-fat-sugar diet with limited daily activities for 5 weeks. The sub-healthy model was successfully established and the feeding conditions were restored. The hyperoxic intervention group (healthy group) were placed in a natural hyperoxic environment for 7 days. The rats feeding status in the spontaneous recovery group were unchanged. The appearance and exhaustive swimming time were compared before and after in healthy rats. Peripheral blood was collected for biochemical measurement. The fluorescence intensity of FXR and peroxisome proliferator activated receptor α (PPAR α) in liver tissue was detected by fluorescence double staining. Real-time fluorescent semi-quantitative PCR and Western blot were used to detect the RNA and protein expression condition of bile acid-FXR signaling pathway related indicators (FXR, PPARα, and SREBP-1c) in liver tissues. Results: Compared with the control group, the model group had gained body weight, and the vitality was decreased, while triglycerides [TG, (1.18 ± 0.20) mmol/L vs. (0.65 ± 0.12) mmol/L] and total cholesterol [TC, (1.23 ± 0.29) mmol/L vs. (1.00 ± 0.25) mmol/L] level was increased, (P < 0.05), which suggests the presence of hepatic steatosis. TG and TC level in the healthy group and spontaneous recovery group were lower than the model group, and the differences between the healthy group and the model group were statistically significant (P < 0.05). Compared with the model group, the expression of FXR and PPARα in the liver of the healthy and the spontaneous recovery group was enhanced, while the expression of the sterol regulatory element binding protein 1c (SREBP-1c) was decreased. FXR and PPARα mRNA levels in the healthy group and the model group were (9.27 ± 0.26 vs. 6.77 ± 0.20), and (9.71 ± 0.21 vs. 7.09 ± 0.24), P < 0.01, respectively. Compared with the model group, spontaneous recovery group mRNA levels were 7.99 ± 0.30 and 8.44 ± 0.28, P < 0.05, respectively. FXR and SREBP-1c protein levels between the healthy group and the model group were (1.30 ± 0.19 vs.0.43 ± 0.28), and (1.56 ± 0.22 vs. 2.43 ± 0.19), P < 0.01, respectively. Compared with the model group, the FXR and SREBP-1c protein levels of the spontaneous recovery group were 0.81 ± 0.33 vs. 2.10 ± 0.38, P < 0.05, respectively. In addition, natural hyperoxic environment had enhanced liver lipid metabolism and improved lipid disorders. Conclusion: The natural hyperoxic environment have the ability to regulate liver lipid metabolism and can improve mild hyperlipidemia to a certain extent.


Assuntos
Ácidos e Sais Biliares , Metabolismo dos Lipídeos , Animais , Ácidos e Sais Biliares/metabolismo , Lipídeos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar
20.
Georgian Med News ; (312): 138-145, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33964842

RESUMO

The article presents the results of biochemical studies of blood and morphological characteristics of liver changes in laboratory animals (rats) under experimental conditions of paracetamol hepatitis and intragastric administration of a new substance G10 from the «Zhuzgun¼ plant in various doses. The obtained data open up prospects for further studies of the pharmacological properties of the substance G10, the possibility of including it as a phytotherapeutic agent in the complex of preventive and therapeutic measures for acute toxic hepatitis. The study of the hepatoprotective properties was conducted in the "Educational and Research Pharmacological Laboratory" of the Department of General Pharmacology of the Astana Medical University. The object of the study was the substance G. 10 from the Juzgun plant, which is a brown powder, odorless, poorly soluble in water. Тhe analysis of the results of our own research allows us to conclude that the substance G10 obtained from the plant «Zhuzgun¼ in various doses has a significant positive effect on the dynamics of biochemical parameters of blood serum in animals with experimental acute paracetamol hepatitis.The results of pathomorphological examination of the internal organs of laboratory animals (rats) with intragastric administration of substance G10 also allow us to conclude that it has a hepatoprotective effect. The results of microscopic and biochemical studies of laboratory animals (rats) in acute toxic hepatitis with a new substance from the plant Calligonum allow us to conclude that the substance G10 has a hepatoprotective property. The obtained preliminary data on the hepatoprotective efficacy of substance G10 open up new prospects for further studies of its pharmacological properties.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Extratos Vegetais , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
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