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1.
BMC Complement Med Ther ; 22(1): 16, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031035

RESUMO

BACKGROUND: Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. METHODS: Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals' relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. RESULTS: There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats' relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium's inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. CONCLUSION: The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.


Assuntos
Aloe/toxicidade , Extratos Vegetais/toxicidade , Animais , Feminino , Dose Letal Mediana , Masculino , Ratos , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Uganda
2.
Prog Orthod ; 23(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978631

RESUMO

BACKGROUND: Constricted maxillary bone is a common skeletal deformity, which may lead to crowding and posterior crossbite. Mid-palatal suture expansion is often used to increase the maxillary width, but its skeletal effects are limited and tend to relapse, even with prolonged retention. We hypothesized that parathyroid hormone (PTH) may reduce the relapse of maxillary expansion. METHODS: We established a novel rat maxillary expansion model using palatal tubes with an insertable "W"-shaped spring which can be repeatedly activated. A total of 32 male healthy Wistar rats were randomly divided into six groups: the control group, the PTH group, the expansion group, the expansion + PTH group, the expansion + relapse group and the expansion + PTH + relapse group. All animals in the first 4 groups were killed after 10 days and the 2 relapse groups were killed after 15 days. The maxillary arch widths and histological staining were used to assess the expansion and relapse effects. The immunohistochemical staining, micro-CT, RT-qPCR and Western blot were used to evaluate the bone remodeling during expansion. RESULTS: The suture width was increased by the expansion device, and the repeated activation maxillary expansion rat model showed better expansion effects than the conventional model. PTH significantly promoted the expansion width and reduced the relapse ratio. Meanwhile, in the expansion + PTH group, histological and immunohistochemical staining showed that osteoblasts, osteoclasts, new cartilage and osteoid were significantly increased, micro-CT showed increased bone mass, and PCR and Western blot results confirmed up-regulation of RANKL, ß-catenin, type II collagen and OCN. CONCLUSION: The novel repeated activation maxillary expansion rat model has better effects than the conventional model. PTH enhances the maxillary expansion and reduces its relapse by regulating Wnt/ß-catenin and RANKL pathways. PTH administration may serve as an adjunctive therapy in addition to mechanical expansion for treatment of maxillary constriction.


Assuntos
Técnica de Expansão Palatina , Hormônio Paratireóideo , Animais , Masculino , Osteoblastos , Osteogênese , Ratos , Ratos Wistar , Recidiva , beta Catenina
3.
Int J Mol Sci ; 23(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35008924

RESUMO

Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium-pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium-pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.


Assuntos
Epilepsia/metabolismo , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Piridinas/farmacologia , Convulsões , Tiazóis/farmacologia , Animais , Comportamento Animal , Modelos Animais de Doenças , Lítio , Masculino , Neurônios/efeitos dos fármacos , Pilocarpina , Ratos , Ratos Wistar , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores
4.
Acta Cir Bras ; 36(11): e361101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35019008

RESUMO

PURPOSE: To compare biological compatibility, hemostasis, and adhesion formation between oxidized regenerated cellulose and lyophilized hydrolyzed porcine collagen in liver trauma. METHODS: Forty male Wistar rats constituted two groups: group A (oxidized cellulose) and group B (lyophilized hydrolyzed collagen). Standardized liver trauma was made, and the hemostatic agent was applied. Animals in subgroups A7 and B7 were submitted to euthanasia and relaparotomy after seven days, and in subgroups A14 and B14 after 14 days. Macroscopic and microscopic results were evaluated. RESULTS: There was no fluid in the cavity in any of the animals, and adhesions were present in all of them. In the analysis after seven days, the adhesions were grades 3 or 4 and consisted of omentum, small intestine, and abdominal wall (p<0.05). In both groups, the mesh was surrounded by a capsule, which was not observed after 14 days. In the evaluation after 14 days, adhesions were grades 2 or 3 (p>0.05). The microscopic examination showed subacute and chronic reactions, in both groups and in both timepoints, with similar frequency. The intensity of fibrosis always presented positive scores. Microabscesses and xanthomatous macrophages were observed in both groups. CONCLUSIONS: There was no superiority of one agent over the other.


Assuntos
Celulose Oxidada , Gelatina , Hemorragia/tratamento farmacológico , Neoplasias Hepáticas , Animais , Celulose Oxidada/uso terapêutico , Gelatina/uso terapêutico , Masculino , Ratos , Ratos Wistar , Suínos , Aderências Teciduais
5.
Braz J Med Biol Res ; 55: e11597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35019034

RESUMO

The effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation associated with exercise training at different intensities and frequencies on skeletal muscle regeneration of muscle-injured rats was investigated. Male Wistar rats were divided into sedentary and trained groups. The sedentary groups were subdivided into non-injured (SED-Ct), non-injured supplemented with HMB (SED-Ct-HMB), injured (SED), and injured with HMB (SED-HMB), and the trained groups were injured, supplemented with HMB, and then divided into training three times a week without load (HT3) or with load (HT3L) and training five times a week without load (HT5) and with load (HT5L). The rats received a daily dose of HMB associated with 60 min of swimming with or without 5% body mass load for 14 days. On the 15th day, cryoinjury was performed in the right tibialis anterior muscle (TA), and 48 h later, supplementation and training continued for 15 days. After the last session, the TA was dissected and a cross-sectional area (CSA) of muscle fibers was used to determine the percentage of CSA fibers and connective tissue (%CT), as well as the total and phosphorylated protein contents. SED-HMB showed increased CSA and decreased %CT and TGF-ß when compared to SED. HT3 showed increased CSA and reduced %CT accompanied by increased IGF-1/Akt, myogenin, and MuRF1, and decreased TGF-ß. The CSA of HT5L also increased, but at the cost of a higher %CT compared to the other groups. Our results demonstrated that HMB associated with training without load and with lower frequency per week may be a valuable strategy for skeletal muscle regeneration.


Assuntos
Músculo Esquelético/crescimento & desenvolvimento , Condicionamento Físico Animal , Regeneração , Valeratos , Animais , Suplementos Nutricionais , Fator de Crescimento Insulin-Like I , Masculino , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Wistar
6.
An Acad Bras Cienc ; 94(1): e20200844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35019002

RESUMO

Aging is characterized by several neurochemical modifications involving structural proteins and neurotransmitters. Exercise has been recognized as an enhancer of overall health; whereas, diphenyl diselenide (PhSe)2 has been reported to have antioxidant, anti-inflammatory, and neuroprotective effects in rodents. A combination of pharmacological and non-pharmacological interventions has been proposed to prevent the aging effects. This study aimed to determine the swimming exercise and (PhSe)2 dietary supplementation synergic effects on the [3H] γ-aminobutyric acid (GABA) uptake in aged rats. Male Wistar rats (24 months) received 1 ppm of (PhSe)2 supplemented in the standard chow for 4 weeks. Rats were subjected to swimming training (20 min per day for 4 weeks). After 4 weeks, the [3H]GABA uptake was determined in samples of cerebral cortex and striatum of rats. The results of the present study demonstrate that the association of (PhSe)2-supplemented diet and swimming exercise was effective against the decrease of cerebral cortical and striatal [3H]GABA uptake in aged rats. The association of (PhSe)2 dietary supplementation with swimming exercise modulated the GABA uptake in cerebral structures of aged rats.


Assuntos
Suplementos Nutricionais , Natação , Animais , Derivados de Benzeno , Córtex Cerebral , Dieta , Masculino , Compostos Organosselênicos , Ratos , Ratos Wistar , Ácido gama-Aminobutírico
7.
AAPS PharmSciTech ; 23(1): 54, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35028813

RESUMO

The purpose of our study was using a computational simulation to develop a long-acting patch of rivastigmine (RVS). A range of patch formulations were screened including pressure sensitive adhesive (PSA), pharmaceutical excipients, and controlled release membranes using transfer simulation based on a mathematical model. Diffusion dynamics parameters for simulated operations were acquired through in vitro release tests (IVRT) and in vitro skin permeation tests (IVPT). The mechanism of controlled release was studied by FTIR (Fourier transform infrared), DSC (differential scanning calorimeter) and molecular docking. Results of a rat in vitro permeation profile showed excellent correlation with the in vivo deconvolution profile (R2=0.998). Experiments testified to transfer of RVS at a relatively uniform speed with high skin permeation (2531.2±142.46 µg/cm2) in 72 h. Pharmacokinetic data obtained in vivo also confirmed stable plasma concentrations over 72 h for the optimized patch, and significant prolongation of both Tmax (11.20±1.79 h) and MRT0-t (33.91±5.33 h). Cmax was controlled with AUC0-t (267.34±24.46 h ng/ml), which was closely comparable to parameters of a commercial Exelon® Patch. The successful development of a long-acting patch of RVS thus underscores the potential of computer aided design in a context of promnesic transdermal delivery. Graphical abstract.


Assuntos
Absorção Cutânea , Adesivo Transdérmico , Administração Cutânea , Animais , Simulação de Acoplamento Molecular , Ratos , Ratos Wistar , Rivastigmina , Pele/metabolismo
8.
Invest Ophthalmol Vis Sci ; 63(1): 4, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34982146

RESUMO

Purpose: Netarsudil, a Rho kinase inhibitor with norepinephrine transport inhibitory effect, lowers intraocular pressure, however, its effect on axon damage remains to be elucidated. The aim of the current study was to investigate the effect of netarsudil on TNF-induced axon loss and to examine whether it affects phosphorylated-AMP-activated kinase (p-AMPK) and autophagy in the optic nerve. Methods: Intravitreal administration of TNF or TNF with netarsudil was carried out on rats and quantification of axon number was determined. Electron microscopy determined autophagosome numbers. Localization of p-AMPK expression was examined by immunohistochemistry. The changes in p62, LC3-II, and p-AMPK levels were estimated in the optic nerve by immunoblot analysis. The effect of an AMPK activator A769662 or an AMPK inhibitor dorsomorphin on axon number was evaluated. Results: Morphometric analysis revealed apparent protection by netarsudil against TNF-induced axon degeneration. Netarsudil increased autophagosome numbers inside axons. Netarsudil treatment significantly upregulated optic nerve LC3-II levels in both the TNF-treated eyes and the control eyes. Increased p62 protein level induced by TNF was significantly ameliorated by netarsudil. The netarsudil administration alone lessened p62 levels. Netarsudil significantly upregulated the optic nerve p-AMPK levels. A769662 exhibited obvious axonal protection against TNF-induced damage. A769662 treatment upregulated LC3-II levels and the increment of p62 level induced by TNF was significantly ameliorated by A769662. Immunohistochemical analysis revealed that p-AMPK is present in axons. Netarsudil-mediated axonal protection was significantly suppressed by dorsomorphin administration. Conclusions: Netarsudil upregulated p-AMPK and autophagy. Netarsudil-mediated axonal protection may be associated with upregulated p-AMPK.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/fisiologia , Axônios/efeitos dos fármacos , Benzoatos/farmacologia , Degeneração Neural/prevenção & controle , Nervo Óptico/efeitos dos fármacos , Fator de Necrose Tumoral alfa/toxicidade , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Axônios/enzimologia , Axônios/patologia , Compostos de Bifenilo/farmacologia , Inibidores Enzimáticos/farmacologia , Imuno-Histoquímica , Injeções Intravítreas , Masculino , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/metabolismo , Degeneração Neural/enzimologia , Nervo Óptico/ultraestrutura , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Pironas/farmacologia , Ratos , Ratos Wistar , Proteína Sequestossoma-1/metabolismo , Tiofenos/farmacologia , beta-Alanina/farmacologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-35010784

RESUMO

Nickel oxide nanoparticles (NiO NPs) are highly redox active nanoparticles. They can cause acute and chronic inflammation in rat lungs. Unlike the gut microbiome, the association between the lung microbiome's role and pulmonary inflammatory response to inhaled nanoparticles remains largely unexplored. We aimed to explore the interaction between the lung microbiome and inflammatory responses in rats exposed to NiO NPs. Thirty female Wistar rats were randomly categorized into control and low- (50 cm2/rat), and high- (150 cm2/rat) dose NiO NPs exposure groups. NiO NPs were intratracheally instilled, and cytological, biochemical, proinflammatory cytokine, and lung microbiome analyses of bronchoalveolar lavage fluid were performed at 1 day and 4 weeks after instillation. NiO NPs caused a neutrophilic and lymphocytic inflammatory response in rat lung. We demonstrated that exposure to NiO NPs can alter the lung microbial composition in rats. In particular, we found that more Burkholderiales are present in the NiO NPs exposure groups than in the control group at 1 day after instillation. Dysbiosis in the lung microbiome is thought to be associated with acute lung inflammation. We also suggested that Burkholderiales may be a key biomarker associated with lung neutrophilic inflammation after NiO NPs exposure.


Assuntos
Nanopartículas Metálicas , Microbiota , Nanopartículas , Animais , Líquido da Lavagem Broncoalveolar , Feminino , Inflamação/induzido quimicamente , Pulmão , Nanopartículas Metálicas/toxicidade , Nanopartículas/toxicidade , Níquel , Ratos , Ratos Wistar
10.
J Physiol Sci ; 72(1): 1, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034601

RESUMO

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 µg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.


Assuntos
Excitação Neurológica , Serotonina , Tonsila do Cerebelo , Animais , Benzimidazóis , Estimulação Elétrica , Masculino , Ratos , Ratos Wistar , Convulsões/tratamento farmacológico
11.
Braz J Med Biol Res ; 55: e11873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35043862

RESUMO

Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.


Assuntos
Barorreflexo , Sepse , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Frequência Cardíaca , Rim , Ratos , Ratos Wistar , Sistema Nervoso Simpático
12.
AAPS PharmSciTech ; 23(1): 46, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34984577

RESUMO

The in vitro dissolution of Avanafil (AVA) is the rate-limiting step for its bioavailability. Also, it undergoes the first-pass metabolism, and its absorption is altered significantly in the presence of food. So, our study aimed to overcome the previous hurdles and improve the AVA bioavailability by its incorporation in the ultra-deformable nanovesicles, transfersomes (TRF), then loading these nanovesicles in transdermal films. The AVA-loaded TRF formulation was optimized using Draper-Lin small composite design (D-LSCD). The optimized AVA-loaded TRF was evaluated for quality attributes and assessed for skin permeation using a fluorescence laser microscope and for pharmacokinetic parameters after topical application on the rats. The optimized AVA-loaded TRF showed a vesicle size of 97.75 nm, a zeta potential of -28.83 mV, and entrapment efficiency of 95.14% with good deformability and release profile. The intense discoloration in the deep skin layers of the rats indicated the permeation efficiency of AVA-loaded TRF films. The pharmacokinetic parameters specified the augmented absorption extent with Cmax of 254.66 ± 8.02 ng/mlversus 70.33 ± 3.05 ng/ml which reflected on the AUC0-inf that has a value of 2050.45 ± 159.14 ng/ml h versus 497.34 ± 102.61 ng/ml h for the optimized AVA-loaded TRF film and raw AVA-loaded film, respectively. These promising results wide open the field for broader clinical application of this alternative delivery pathway for superior bioavailability, efficacy, and patient compliance and satisfaction.


Assuntos
Sistemas de Liberação de Medicamentos , Pirimidinas/administração & dosagem , Absorção Cutânea , Adesivo Transdérmico , Administração Cutânea , Animais , Disponibilidade Biológica , Tamanho da Partícula , Ratos , Ratos Wistar , Pele/metabolismo
13.
In Vivo ; 36(1): 221-226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972718

RESUMO

BACKGROUND/AIM: Intestinal anastomosis' integrity is crucial in surgery. This study aimed to investigate whether fibrin glue (FG) (a fibrin sealant containing human factor XII and fibrinogen) has a positive effect on the healing and the integrity of the ileoileal anastomosis in rats. MATERIALS AND METHODS: Twenty Wistar rats underwent enterotomy, ileoileal anastomosis and divided into four groups (A: complete anastomosis-no FG, B: complete anastomosis-FG, C: incomplete anastomosis-no FG, D: incomplete anastomosis-FG). Data included leak, adhesions, bursting pressure of the anastomosis, neoangiogenesis, and hydroxyproline levels. RESULTS: Angiogenesis was significantly higher in group B compared to group A (p=0.019). There were no significant differences between groups A and B regarding adhesions, hydroxyproline, and bursting pressure (p=0.500, p=0.158 and p=0.829, respectively). Hydroxyproline levels were higher in group D compared to C, but did not reach significance (p=0.098). CONCLUSION: Fibrin glue has a positive effect on ileoileal anastomoses. It is not entirely clear whether this effect is due to mechanical support or to the facilitation of the healing process or both. Further research is needed before FG can be applied to humans.


Assuntos
Colo , Adesivo Tecidual de Fibrina , Anastomose Cirúrgica , Animais , Colo/cirurgia , Adesivo Tecidual de Fibrina/farmacologia , Ratos , Ratos Wistar , Cicatrização
14.
BMC Complement Med Ther ; 22(1): 4, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983490

RESUMO

BACKGROUND: Though Lippia javanica (Burm.f.) Spreng antioxidant activity has been demonstrated, its effect in protecting the brain from lead (Pb)-induced oxidative damage is unknown. This study investigated the effect of L. javanica against Pb-induced oxidative stress, inflammation, apoptosis and acetylcholinesterase activity in rat's brain. METHODS: L. javanica herbal tea infusion was prepared, its phytochemical constituent was revealed by liquid chromatography-Mass spectrometer (LC-MS) and was administered simultaneously with Pb. Four groups of male Wistar rats (n = 5/group) were used: control received distilled water; Pb-acetate group received 50 mg Pb/ Kg bodyweight (bw), treatment group received 50 mg Pb/ Kg Pb-acetate + 5 ml/kg bw L. javanica and L. javanica group received 5 ml/Kg bw of L. javanica tea infusion only. After 6 weeks of treatment, oxidative status, acetylcholinesterase activity, inflammation and apoptosis was assessed in brain tissue which was also histologically examined. RESULTS: Mean brain and heart weight was reduced (p < 0.05) while liver and spleen weights were increased (p < 0.05) in Pb exposed animals but were prevented by L. juvanica treatment. Treatment with L. javanica increased (p < 0.05) overall brain antioxidant status (glutathione and superoxide dismutase activities) and reduced lipid peroxidation (p < 0.05) compared to the Pb exposed animals. Pro-inflammatory cytokine tumour necrotic factor-alpha, pro-apoptosis Bax protein and anticholinesterase activity were reduced (p < 0.05) in Pb-L. javanica treated animals compared to the Pb exposed group. Histological examination confirmed neuroprotective effects of L. javanica as evidenced by reduced apoptosis/necrosis and inflammation-induced vacuolization and oedema in the hippocampus. The L. javanica treatment alone had no detrimental effects to the rats. LC-MS analysis revealed L. javanica to be rich in phenolics. CONCLUSIONS: This study demonstrated that L. javanica, rich in phenolics was effective in reducing Pb-induced brain oxidative stress, inflammation, apoptosis, acetylcholinesterase activity and neuronal damage.


Assuntos
Encéfalo/metabolismo , Chumbo/efeitos adversos , Lippia/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Chás de Ervas , Animais , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
15.
Acta Cir Bras ; 36(12): e361203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35019065

RESUMO

PURPOSE: To evaluate whether using platelet-rich plasma (PRP) in the graft recipient bed after the resection of a neoplasia can influence its recurrence because this product stimulates angiogenesis, mitogenesis and chemotaxis. METHODS: A study with 30 rats Wistar (Rattus norvegicus albinus), which were separated into group A (induction of carcinogenesis, PRP in the postoperative period) and group B (induction of carcinogenesis, absence of PRP in the postoperative period), with 15 animals in each. Carcinogenesis was induced on the skin of the animals' chest by the topical application of 0.5% dimethylbenzantracene (DMBA) diluted in acetone. After surgical resection of the induced neoplasia, PRP was used to stimulate angiogenesis before surgical wound synthesis. Data on the control and experimental groups and macroscopic and microscopic variables were evaluated using analysis of variance and the Tukey's test (5%). RESULTS: It was possible to determine that the use of PRP is good in reconstructive surgeries, but it is contraindicated in patients during tumor resection, as it can cause changes in the surgical bed, in addition to stimulating recurrences and metastases. CONCLUSIONS: PRP may interact with tumour cells that were in the recipient site of the surgical wound during the resection of a neoplasia, and a local recurrence process can be triggered by applying this product.


Assuntos
Plasma Rico em Plaquetas , Neoplasias Cutâneas , Animais , Humanos , Ratos , Ratos Wistar , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/cirurgia , Transplante de Pele , Cicatrização
16.
Environ Pollut ; 296: 118729, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34953950

RESUMO

Glyphosate-based herbicides (GBHs) are the agrochemicals most used around the globe. However, they might have adverse effects on human and animal health. Previously, we showed that female rats neonatally exposed to GBHs exhibit altered expression of morphogenetic molecules and biomarkers of uterine development. We also observed a reduction in the size of implantation sites, altered expression of decidualization-related molecules, and increased post-implantation losses. Since decidualization comprises morphogenetic, biochemical and vascular changes, here we investigated the effects of neonatal GBH exposure on uterine angiogenesis in neonatal and pregnant rats. To achieve this, Wistar female rats were exposed to saline solution or GBH (2 mg glyphosate/kg-bw/day) on post-natal days (PND) 1, 3, 5 and 7. On PND8, uterine samples were collected for developmental studies. On PND90, the remaining females were mated and in the morning of gestational day (GD) 9, the implantation sites were collected. Angiogenesis-related molecules and cells involved in this process were identified and/or measured by immunohistochemistry or RT-PCR. On PND8, GBH-treated rats showed increased vascular endothelial growth factor (VEGF) expression and decreased Notch1, inducible nitric oxide synthase (iNOS) and Angiopoietin-2 (Ang2) mRNA levels. Vascular area, vessel diameter, endothelial cell proliferation, VEGF and Nestin protein expression, and VEGF, Notch1, iNOS and cyclooxygenase-2 (Cox-2) genes were downregulated in implantation sites of exposed females, while Ang2, VEGF receptor 1 and interleukin-10 (IL-10) were increased. Mast cells and macrophages were increased on PND8 and GD9 of treated rats. The increased Transforming growth factor-beta expression in the antimesometrial zone and IL-10 mRNA expression suggest that the M2 type is the predominant population of macrophages on implantation sites. In conclusion, neonatal GBH exposure alters the expression of angiogenesis-related molecules at neonatal uterine development and decidual reaction, suggesting altered vascular support. These alterations might contribute to the increased post-implantation losses observed in GBH-treated rats.


Assuntos
Herbicidas , Animais , Feminino , Glicina/análogos & derivados , Glicina/toxicidade , Herbicidas/toxicidade , Gravidez , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular
17.
Phytother Res ; 36(1): 488-505, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34939704

RESUMO

This study targeted to examine the protective effects of acetovanillone (AV) against methotrexate (MTX)-induced hepatotoxicity. Thirty-two rats were allocated into four groups of eight animals; Group 1: Normal; Group 2: administered AV (100 ml/kg; P.O.) for 10 days; Group 3: challenged with MTX (20 mg/kg, i.p; single dose); Group 4: administered AV 5 days before and 5 days after MTX. For the first time, this study affords evidence for AV's hepatoprotective effects on MTX-induced hepatotoxicity. The underlined mechanisms behind its hepatic protection include counteracting MTX-induced oxidative injury via down-regulation of NADPH oxidase and up-regulation of Nrf2/ARE, SIRT1, PPARγ, and cytoglobin signals. Additionally, AV attenuated hepatic inflammation through down-regulation of IL-6/STAT-3 and NF-κB/AP-1 signaling. Network pharmacology analysis exhibited a high enrichment score between the interacting proteins and strongly suggested the intricate and essential role of the target proteins regulating MTX-induced oxidative damage and inflammatory perturbation. Besides, AV increased the in vitro cytotoxic activity of MTX toward PC-3, HeLa, and K562 cancer cell lines. On the whole, our investigation suggested that AV might be regarded as a promising adjuvant for the amelioration of MTX hepatotoxicity and/or increased its in vitro antitumor efficacy, and it could be used in patients receiving MTX.


Assuntos
Fator 2 Relacionado a NF-E2 , NF-kappa B , Acetofenonas , Animais , Humanos , Interleucina-6 , Metotrexato/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Fator de Transcrição AP-1
18.
J Pharmacol Toxicol Methods ; 113: 107144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34896263

RESUMO

The development of a stable disease model with an adequate biochemical profile is crucial for the preclinical investigation of new antidiabetic agents. This study aimed at optimization and characterization of high fat diet (HFD) fed streptozotocin (STZ) induced type 2 diabetes mellitus (type 2 DM) Wistar rat model. Wistar rats fed with HFD for four weeks received STZ (30, 40, and 50 mg/kg, intraperitoneal). Diabetic rats were observed for four more weeks and sacrificed. Non- injected healthy Wistar rats and HFD-fed rats were used as control groups. The glucose status and the lipid profile of the model were assessed. STZ-induced rats showed significant dose-dependent alterations in fasting serum insulin and glucose, homeostatic model assessment- insulin resistance (HOMA-IR), HOMA- ß cell function (HOMA- ß), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglycerides (TG) and atherogenic index (AI). STZ 50 mg/kg group rats showed significant increase in glycated hemoglobin (HbA1c), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) levels compared to healthy rats. The atherogenic risk index (ARI), the Castelli risk index-I (CRII), and CRI-II were significantly (p < 0.05) high in the STZ 40 mg/kg and 50 mg/kg group rats. Results suggest that the Wistar rats fed with HFD rich in saturated fat for four weeks followed by a single intraperitoneal dose of 50 mg/kg of STZ would produce a stable diabetic model which closely mimic biochemical features of type 2 DM. Key messages: Wistar rats fed with HFD rich in saturated fat for four weeks followed by a single intraperitoneal dose of 50 mg/kg STZ would produce a stable diabetic model that closely mimics the biochemical characteristics of type 2 DM characterized by insulin resistance, relative insulin deficiency and impaired ß cell function.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Glicemia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Dieta Hiperlipídica/efeitos adversos , Hipoglicemiantes , Ratos , Ratos Wistar , Estreptozocina
19.
J Clin Neurosci ; 95: 106-111, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929632

RESUMO

Alzheimer's disease (AD) is a type of brain dysfunction featuring a gradual loss in memory. This study aimed to determine the effect of 4 weeks of aerobic rehabilitation exercise (RhExe) on the genes expression of BDNF and TGF-ß1 in the hippocampus tissue of rats with the AD induced by injection of amyloid-beta (Aß1-42). Twenty-one male Wistar rats were randomly divided into 3 groups: Aß injection (n = 7), Aß + exercise (n = 7) and control (n = 7). AD was induced by a single dose of Aß injection into the hippocampus of rats. Three days after surgery, the Aß + exercise group experienced four weeks of the RhExe (5 days/week). Forty-eight hours after the last training session, the animals underwent the Morris water maze test. The animals were sacrificed 24 h after the test, and hippocampal tissue was split. The mRNA expression of BDNF, TGF-ß1, and TGF-ß1 II receptors was measured. The TGF-ß1 and TGF-ß1 II receptor genes expression of Aß + exercise group were significantly higher than the Aß injection group (P ≤ 0.001). BDNF gene expression in the hippocampus of the Aß + exercise group was significantly higher than the Aß injection group (P ≤ 0.001). Spatial memory was significantly higher in the Aß + exercise group than in the Aß injection group (p ≤ 0.01). It seems that aerobic exercise can counteract the harmful effects of Aß through the BDNF and TGF-ß1molecular signaling pathways.


Assuntos
Doença de Alzheimer , Fator Neurotrófico Derivado do Encéfalo , Hipocampo , Fator de Crescimento Transformador beta1 , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Hipocampo/metabolismo , Masculino , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Wistar
20.
Exp Neurol ; 347: 113900, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34695425

RESUMO

During the pathogenesis of Parkinson's disease (PD), aggregation of alpha-synuclein (αSyn) induces a vicious cycle of cellular impairments that lead to neurodegeneration. Consequently, removing toxic αSyn aggregates constitutes a plausible strategy against PD. In this work, we tested whether stimulating the autolysosomal degradation of αSyn aggregates through the Ras-related in brain 7 (Rab7) pathway can reverse αSyn-induced cellular impairment and prevent neurodegeneration in vivo. The disease-related A53T mutant of αSyn was expressed in primary neurons and in dopaminergic neurons of the rat brain simultaneously with wild type (WT) Rab7 or the T22N mutant as negative control. The cellular integrity was quantified by morphological and biochemical analyses. In primary neurons, WT Rab7 rescued the αSyn-induced loss of neurons and neurites. Furthermore, Rab7 decreased the amount of reactive oxygen species and the amount of Triton X-100 insoluble αSyn. In rat brain, WT Rab7 reduced αSyn-induced loss of dopaminergic axon terminals in the striatum and the loss of dopaminergic dendrites in the substantia nigra pars reticulata. Further, WT Rab7 lowered αSyn pathology as quantified by phosphorylated αSyn staining. Finally, WT Rab7 attenuated αSyn-induced DNA damage in primary neurons and rat brain. In brief, Rab7 reduced αSyn-induced pathology, ameliorated αSyn-induced neuronal degeneration, oxidative stress and DNA damage. These findings indicate that Rab7 is able to disrupt the vicious cycle of cellular impairment, αSyn pathology and neurodegeneration present in PD. Stimulation of Rab7 and the autolysosomal degradation pathway could therefore constitute a beneficial strategy for PD.


Assuntos
Neurônios Dopaminérgicos/metabolismo , alfa-Sinucleína/biossíntese , alfa-Sinucleína/toxicidade , /farmacologia , Animais , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
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