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1.
Naunyn Schmiedebergs Arch Pharmacol ; 394(11): 2273-2287, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34468816

RESUMO

Morbidity and mortality risks are enhanced in preeclamptic (PE) mothers and their offspring. Here, we asked if sexual dimorphism exists in (i) cardiovascular and renal damage evolved in offspring of PE mothers, and (ii) offspring responsiveness to antenatal therapies. PE was induced by administering NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, oral gavage) to pregnant rats for 7 days starting from gestational day 14. Three therapies were co-administered orally with L-NAME, atrasentan (endothelin ETA receptor antagonist), terutroban (thromboxane A2 receptor antagonist, TXA2), or α-methyldopa (α-MD, central sympatholytic drug). Cardiovascular and renal profiles were assessed in 3-month-old offspring. Compared with offspring of non-PE rats, PE offspring exhibited elevated systolic blood pressure and proteinuria and reduced heart rate and creatinine clearance (CrCl). Apart from a greater bradycardia in male offspring, similar PE effects were noted in male and female offspring. While terutroban, atrasentan, or α-MD partially and similarly blunted the PE-evoked changes in CrCl and proteinuria, terutroban was the only drug that virtually abolished PE hypertension. Rises in cardiorenal inflammatory (tumor necrosis factor alpha, TNFα) and oxidative (isoprostane) markers were mostly and equally eliminated by all therapies in the two sexes, except for a greater dampening action of atrasentan, compared with α-MD, on tissue TNFα in female offspring only. Histopathologically, antenatal terutroban or atrasentan was more effective than α-MD in rectifying cardiac structural damage, myofiber separation, and cytoplasmic alterations, in PE offspring. The repair by antenatal terutroban or atrasentan of cardiovascular and renal anomalies in PE offspring is mostly sex-independent and surpasses the protection offered by α-MD, the conventional PE therapy.

2.
Toxicol Appl Pharmacol ; 426: 115615, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34102242

RESUMO

Current therapies for preeclampsia (PE) and its complications are limited and defective. Considering the importance of endothelin (ET) and thromboxane A2 (TXA2) signaling in PE pathophysiology, we tested the hypothesis that prenatal blockade of endothelin ETA or thromboxane TXA2 receptors favorably reprograms preeclamptic cardiovascular and renal insults. PE was induced by daily oral administration of L-NAME (50 mg/kg) to pregnant rats for 7 consecutive days starting from gestational day 14. The effects of co-exposure to atrasentan (ETA receptor blocker, 10 mg/kg/day) or terutroban (TXA2 receptor blocker, 10 mg/kg/day) on cardiovascular and renal anomalies induced by PE were assessed on gestational day 20 (GD20) and at weaning time and compared with those evoked by the sympatholytic drug α-methyldopa (α-MD, 100 mg/kg/day), a prototypic therapy for PE management. Among all drugs, terutroban was basically the most potent in ameliorating PE-evoked increments in blood pressure and decrements in creatinine clearance. Cardiorenal tissues of PE rats exhibited significant increases in ETA and TXA2 receptor expressions and these effects disappeared after treatment with atrasentan and to a lesser extent by terutroban or α-MD. Atrasentan was also the most effective in reversing the reduced ETB receptor expression in renal tissues of PE rats. Signs of histopathological damage in cardiac and renal tissues of PE rats were mostly improved by all therapies. Together, pharmacologic elimination of ETA or TXA2 receptors offers a relatively better prospect than α-MD in controlling perinatal cardiorenal irregularities sparked by PE.


Assuntos
Atrasentana/uso terapêutico , Antagonistas do Receptor de Endotelina A/uso terapêutico , Cardiopatias/prevenção & controle , Nefropatias/prevenção & controle , Naftalenos/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Propionatos/uso terapêutico , Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores , Animais , Atrasentana/farmacologia , Antagonistas do Receptor de Endotelina A/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cardiopatias/genética , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/genética , Nefropatias/patologia , Nefropatias/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Naftalenos/farmacologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Propionatos/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor de Endotelina A/genética , Receptores de Tromboxano A2 e Prostaglandina H2/genética
3.
Nanomedicine (Lond) ; 16(15): 1281-1296, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34013783

RESUMO

Aim: Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer's disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We investigated the pharmacodynamics and pharmacokinetics of 2-week intranasal galantamine-bound chitosan nanoparticles (G-NP) treatment in scopolamine-induced Alzheimer's disease rat model. Materials & methods: Behavioral, neurobiochemical and histopathological changes were assessed and compared with oral and nasal solutions. Brain uptake and pharmacokinetics were determined using a novel validated LC/MS assay. Results: G-NP enhanced spatial memory, exploring behavior and cholinergic transmission in rats. Beta-amyloid deposition and Notch signaling were suppressed and the histopathological degeneration was restored. G-NP potentiated galantamine brain delivery and delayed its elimination. Conclusion: G-NP hold promising therapeutic potentials and brain targeting, outperforming conventional galantamine therapy.


Assuntos
Doença de Alzheimer , Nanopartículas , Administração Intranasal , Doença de Alzheimer/tratamento farmacológico , Animais , Inibidores da Colinesterase/uso terapêutico , Galantamina/uso terapêutico , Ratos
4.
BMC Pharmacol Toxicol ; 22(1): 24, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933169

RESUMO

BACKGROUND: Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. The acetylcholinesterase inhibitor (ACHEI); neostigmine, is known clinically for its analgesic effect in the perioperative phases proving high efficacy; besides possessing anti-inflammatory properties controlling immune cells and cytokine level. Hence, this study evaluated and compared the analgesic and anti-inflammatory activities of the combination of selective Cox-2 inhibitor; celecoxib, with neostigmine versus a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats. METHODS: Analgesic activity of neostigmine with/without diclofenac or celecoxib was assessed in female Sprague-Dawely rats using the tail clip model and acetic acid induced writhing. Serum level of ß-endorphin was assessed after the tail clip test. The anti-inflammatory activity was evaluated using acute and sub-chronic formalin induced paw edema. At the end of the sub-chronic formalin test, blood samples were collected for analysis of anti-inflammatory, liver and kidney function markers. Livers, kidneys and hind paws were also examined histopathologically. RESULTS: Addition of neostigmine to selective or non-selective NSAIDs (celecoxib or diclofenac) causes an increased level of analgesia of NSAIDs with rapid onset of action and short duration, while causing potentiation of the anti-inflammatory effect of neostigmine as seen in the tail clip, writhing, formalin test, Cox-1 and Cox-2 activities, serum ß-endorphin, TNF-α, NF-кB and HS-CRP. All combinations of this study disturb some kidney and liver functions, however with normal histopathological appearances, while hind paws reveal improved inflammatory infiltration in all treated groups. CONCLUSIONS: Selective and non-selective NSAIDs examined in this study could be good adjunct options to general anesthetic agents and neostigmine in perioperative stages, an outcome that needs further clinical investigations.

5.
Int J Pharm ; 601: 120564, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33812970

RESUMO

Genistein (Gen) is one of the most potent soy isoflavones used for hepatocellular carcinoma (HCC) treatment. Low aqueous solubility and first-pass metabolism are the main obstacles resulting in low Gen oral bioavailability. The current study aims to introduce phytosomes as an approach to improve Gen solubility, protect it from metabolism by complexation with phospholipids (PL), and get used to PL in Gen lymphatic delivery. Different forms of PL namely: Lipiod® S100, Phosal® 53 MCT, and Phosal®75 SA were used in phytosomes preparation GP, GPM, and GPL respectively. The effect of formulation components on Gen absorption, metabolism, and liver accumulation was evaluated following oral administration to rats. Cytotoxicity and cellular uptake studies were applied on HepG2 cells and in-vivo anti-tumor studies were applied to the DEN-mice model. Results revealed that GP and GPL remarkably accumulated Gen aglycone in hepatic cells and minimized the metabolic effect on Gen. They significantly increased the intracellular accumulation of Gen in its complex form in HepG2 cells. Their cytotoxicity is time-dependent according to the complex stability. The enhanced in-vivo anti-tumor effect was observed for GP and GPL compared to Gen suspension on DEN-induced HCC in mice. In conclusion, Gen-phytosomes can represent a promising approach for liver cancer treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Genisteína , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Ratos , Solubilidade
6.
Life Sci ; 277: 119459, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836162

RESUMO

AIMS: The fact that physical activity besides central cholinergic enhancement contributes in improving neuronal function and spastic plasticity, recommends the use of the anticholinesterase and cholinergic drug galantamine with/without exercise in the management of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). MATERIALS AND METHODS: Sedentary and 14 days exercised male Sprague Dawley rats were subjected to EAE. Hereafter, exercised rats continued on rotarod for 30 min for 17 consecutive days. At the onset of symptoms (day 13), EAE sedentary/exercised groups were subdivided into untreated and post-treated with galantamine. The disease progression was assessed by EAE score, motor performance, and biochemically using cerebrospinal fluid (CSF). Cerebellum and brain stem samples were used for histopathology and immunohistochemistry analysis. KEY FINDINGS: Galantamine decreased EAE score of sedentary/exercised rats and enhanced their motor performance. Galantamine with/without exercise inhibited CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6), and Bcl-2-associated X protein (Bax), besides caspase-3 and forkhead box P3 (Foxp3) expression in the brain stem. Contrariwise, it has elevated CSF levels of brain derived neurotrophic factor (BDNF) and B-cell lymphoma (Bcl-2) and enhanced remyelination of cerebral neurons. Noteworthy, exercise boosted the drug effect on Bcl-2 and Bax. SIGNIFICANCE: The neuroprotective effect of galantamine against EAE was associated with anti-inflammatory and anti-apoptotic potentials, along with increasing BDNF and remyelination. It also normalized regulatory T-cells levels in the brain stem. The impact of the add-on of exercise was markedly manifested in reducing neuronal apoptosis.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Galantamina/farmacologia , Animais , Apoptose , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/metabolismo , Galantamina/metabolismo , Masculino , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Neurônios/patologia , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Esforço Físico/fisiologia , Ratos , Ratos Sprague-Dawley
7.
Int J Pharm ; 592: 120091, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33197564

RESUMO

The article presents an experimental study on the possible repurposed use of valsartan (Val), in the local treatment of uncontrolled diabetic foot ulcer. Solid lipid nanoparticles (SLN), loaded with Val were prepared by applying 32 full factorial design using modified high shear homogenization method. The lipid phase composed of Precirol® ATO 5 (P ATO 5) and/or Gelucire 50/13 (G 50/13) in different ratios and a nonionic emulsifier, Pluronic 188 (P188), was used in different percentages. Optimized formulation was further integrated in hydroxyl propyl methyl cellulose (HPMC) gel for the ease of administration. In-vitro and in-vivo characterizations were investigated. The prepared nanoparticles showed small particle size, high entrapment efficiency and sustained drug release. Microbiologically, Val-SLN showed a prominent decrease in the biofilm mass formation for both gram-positive and gram-negative bacteria, as well as a comparable minimum inhibitory concentration level to levofloxacin alone. Diabetes was induced in 32 neonatal Sprague-Dawley rats. At 8 weeks of age, rats with blood sugar level >160 were subjected to surgically induced ulcer. Treatment with Val-SLN for 12 days revealed enhanced healing characteristics through cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nitric oxide (NO), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMPs) and vascular endothelial growth factor (VEGF) pathways. Histological examination revealed re-epithelization in Val-SLN treated ulcer, as well as decrease in collagen using trichrome histomorphometric analysis.


Assuntos
Diabetes Mellitus , Pé Diabético , Nanopartículas , Animais , Antibacterianos , Pé Diabético/tratamento farmacológico , Portadores de Fármacos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hidrogéis , Lipídeos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Valsartana , Fator A de Crescimento do Endotélio Vascular
8.
Life Sci ; 259: 118250, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32791152

RESUMO

AIMS: Several microbial toll-like receptor (TLR) ligands, bacterial DNA and bacterial cell wall fragments have been identified in the synovium of rheumatoid arthritis (RA) patients, proving bacterial involvement in the pathogenesis of RA. The current study aimed to verify that low dose polymyxin B could prevent the development of chronic inflammatory arthritis. METHODS: Twelve days post adjuvant injection, Sprague-Dawley rats were treated twice weekly with methotrexate (0.5 mg/kg) or daily with polymyxin B (1 mg/kg) or with combination of both for 1 or 2 weeks. Arthritis progression was assessed by hind paw swelling, serum levels of tumor growth factor-1ß (TGF-1ß), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (HS-CRP) and nuclear factor kappa B (NF-κB) were measured using ELISA. Cyclooxygenase-1 (Cox-1) and Cox-2 activities, as well as mRNA expression of TLR-2 and TLR-4 were determined. Histopathological examination of the ankle joint was performed as well as immunohistochemistry for anti-TLR-4. Histopathological assessment of toxic effects on the kidney was performed. KEY FINDINGS: Adjuvant arthritis led to a significant swelling of the hind paw and alteration in all serum parameters, TLR-2 and TLR-4 expression, as well as Cox-2 activity. These alterations were associated with histopathological changes of the joints. Polymyxin B reduced significantly all biomarkers of inflammation, showing better effect of the combination in most of the studied parameters, with minimal signs of nephrotoxicity. SIGNIFICANCE: In conclusion, results showed that polymyxin B possesses significant anti-arthritic activity which may be attributed to inhibition of the TLR-4, NF-κB and Cox-2 signaling pathway.


Assuntos
Artrite Experimental/tratamento farmacológico , Polimixina B/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Experimental/fisiopatologia , Artrite Reumatoide/tratamento farmacológico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/fisiologia , Adjuvante de Freund/farmacologia , Inflamação/tratamento farmacológico , Masculino , NF-kappa B/metabolismo , Polimixina B/metabolismo , Polimixina B/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/metabolismo , Receptores Toll-Like/metabolismo , Receptores Toll-Like/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
9.
Eur J Pharmacol ; 883: 173315, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621912

RESUMO

The acetylcholinesterase inhibitor, galantamine, has shown therapeutic effect in rat model of rheumatoid arthritis. Hence, the current study aims at determining the mode of action of galantamine by examining different synovium-derived microRNAs (miRs) and their related pathogenic pathways. The study also focuses on how parasympathetic and sympathetic pathways in the synovial tissue could affect the mode of action and anti-arthritic effect of galantamine. Chemical sympathectomy was initiated in 12 adjuvant arthritic rats by exposure to 6-hydroxydopamine (6-OHDA; 2 × 50 mg/kg) on day 9 after adjuvant injection and again (2 × 100 mg/kg) one week later. Six rats were treated with galantamine (2.5 mg/kg/day) to explore the influence of sympathetic impairment on galantamine effect. Another twelve additional adjuvant arthritic rats were exposed to the selective α7 nicotinic acetylcholine receptor blocker methylcaconitine citrate (MLA; 5.6 mg/kg/day), 15 min before galantamine treatment. As control, six adjuvant arthritic rats were treated with galantamine alone. Treatment proceeded for 5 days, from day 14 till day 18 post-adjuvant injection. Different miRs and their related pathogenic pathways were examined. Tyrosine hydroxylase (TH) expression was also measured in joint tissue. Galantamine affected the expression of the different miRs and their related parameters. Both, 6-OHDA and MLA, interrupted the anti-inflammatory/anti-arthritic effect of galantamine to different extent. Additionally, TH expression in the synovium was affected by galantamine, suggesting a novel pathogenic target in the treatment of rheumatoid arthritis.


Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Galantamina/farmacologia , MicroRNAs/metabolismo , Sistema Nervoso Parassimpático/efeitos dos fármacos , Simpatectomia Química , Membrana Sinovial/efeitos dos fármacos , Animais , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Regulação da Expressão Gênica , Masculino , MicroRNAs/genética , Antagonistas Nicotínicos/farmacologia , Oxidopamina/farmacologia , Sistema Nervoso Parassimpático/metabolismo , Sistema Nervoso Parassimpático/fisiopatologia , Ratos Sprague-Dawley , Simpatolíticos/farmacologia , Membrana Sinovial/inervação , Membrana Sinovial/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
10.
Exp Ther Med ; 19(1): 384-392, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31853315

RESUMO

The current study focused on the effect of creatine supplementation with/without exercise on the expression of genes controlling mitochondrial biogenesis in skeletal and cardiac muscles, as well as its safety profile on the liver and kidney. A total of 40 male Wister rats were included in the present study. Two unexercised groups: The control sedentary group and the sedentary creatine-treated group (n=10) were treated daily with oral creatine (0.5 g/kg per day). Two exercised groups performed swimming exercise training 5 days/week for a period of 5 weeks; The Exercise training group, and exercise training and creatine (0.5 g/kg per day) treated group. After sacrifice, blood samples, cardiac and soleus muscles were collected for assessment of mtDNA copy number, gene expression analysis and nuclear extraction for the assay of PGC-1α. The results of the current study demonstrated that, physical activity with short-term creatine supplementation increased all factors of mitochondrial biogenesis, an effect that is devoid of any kidney or liver adverse effects. Further studies are still required to explore the potential of creatine supplementation in ameliorating mitochondrial diseases, including epilepsy, skeletal and cardiac myopathies, hepatopathies and nephropathies.

11.
Biochem Pharmacol ; 170: 113665, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606410

RESUMO

OBJECTIVE: The evolution of the "cholinergic anti-inflammatory pathway" and the fact that the α 7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is present in the spleen, joint and on the surface of lymphocytes, opened up the prospective in this study of targeting the α7nAChR by the anticholinesterase and cholinergic drug, galantamine, to control inflammation in rheumatoid arthritis (RA). METHODS: Twelve-adjuvant arthritic rats were exposed to the selective α7nAChR blocker methylcaconitine citrate 15 min before galantamine treatment. As control, six adjuvant arthritic rats were treated with galantamine and six others were untreated. After five days TNF-α levels were assessed in spleen and joints, while reduced glutathione was measured in blood and joint tissue. In the second part, magnetically sorted CD4 + T cells from peripheral blood mononuclear cells of RA patients and healthy donors were used to sort CD4 + CD25 - primary T cells (Tresp) and CD4 + CD25 + CD127low Tregs. The suppressive function of Tregs was investigated after incubation with galantamine using flow cytometry. Cell culture supernatants were analyzed for TNF-α and IL-10 levels after three days incubation period of Tregs with Tresp. The effect of galantamine on Tregs was then blocked by α-Bungarotoxin and the same assay has been repeated. RESULTS & CONCLUSION: Selective α7nAChR blockade interrupted the anti-inflammatory effect of galantamine in the spleen and joints of arthritic rats. In healthy donors, galantamine could strengthen the suppressive activity of Tregs; while in RA patients it did not modulate the function of Tregs significantly. Further studies are necessary to investigate whether modulation of the cholinergic nervous system, especially α7nAChR, could have impact on the disturbed immune system in RA, which may open up a new treatment option of autoimmune diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Galantamina/uso terapêutico , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Receptor Nicotínico de Acetilcolina alfa7/fisiologia , Animais , Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Artrite Experimental/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Galantamina/farmacologia , Humanos , Masculino , Antagonistas Nicotínicos/farmacologia , Ratos , Ratos Sprague-Dawley , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
12.
Int J Pharm ; 565: 70-82, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31054878

RESUMO

Post-operative adhesion is a common cause of several complications including intestinal obstruction, chronic pelvic pain and/or infertility. Adhesions are fibrous bands that result from the inflammatory reactions due to peritoneum damage. The current study focused on designing an effective anti-inflammatory loaded barrier for the prevention of post-operative adhesions. The proposed method is based on the use of polyvinyl alcohol (PVA), cryobarrier loaded with Ibuprofen (Ibu). Anti-adhesive Ibu-cryobarriers were prepared in different forms, and subjected to in-vitro evaluation comprising; drug release rate, maximum swelling index, morphological examination using scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FTIR) and mechanical properties. Optimized cryobarriers were further investigated for their in-vivo effectiveness in preventing post-operative adhesions in female Sprague-Dawley rats. All formulations showed appropriate physical and morphological characteristics, in-vitro controlled sustained drug release profiles during a period of seven days with acceptable maximum swelling index. Invivo, all cryobarriers were equivalent to each other concerning serum or tissue parameter. However, morphological and histopathological evaluations revealed that both xerocryogel and lyophilized cryofilms are more effective than the cryogel in prevention of post-operative peritoneal adhesions. The current study showed the possibility of preparing drug loaded cryobarriers using simple technique with an effective in vivo post-operative adhesion prevention.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Criogéis/administração & dosagem , Ibuprofeno/administração & dosagem , Álcool de Polivinil/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Parede Abdominal/cirurgia , Animais , Ceco/cirurgia , Preparações de Ação Retardada/administração & dosagem , Feminino , Ratos Sprague-Dawley
13.
Eur J Pharmacol ; 764: 547-553, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26189022

RESUMO

Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF-α, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Galantamina/farmacologia , Articulações/efeitos dos fármacos , Parassimpatomiméticos/farmacologia , Animais , Artrite Experimental/sangue , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/imunologia , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Adjuvante de Freund , Mediadores da Inflamação/sangue , Isoxazóis/farmacologia , Articulações/imunologia , Articulações/metabolismo , Articulações/patologia , Leflunomida , Masculino , Mycobacterium/imunologia , Radiografia , Ratos Sprague-Dawley , Fatores de Tempo
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