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1.
J Nanosci Nanotechnol ; 20(2): 680-691, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383063

RESUMO

BN has important roles in several physiological events, including bone growth and immune system. New infection-free cranioplasty and has an osteogenic activities material that are compatible with tissue are being developed. We aimed in our study to examine whether different combinations of Boron-nitride/Hydroxyapatite are embedded into the scaffold in the treatment of calvarial defects. 200 adult female Sprague-Dawley rats divided into 10 equal groups. Osteotomy was made by trepan drill in 8 mm diameter. The scaffolds were placed in the rats and were left to recovery for 2 months. During the experiment, CT scans were taken from the calvarial areas of the rats in the 2nd, 4th and 8th weeks. Significant healing was observed in defect diameters in 2.5% BN+10% HA, 2.5% BN and 5% BN+10% HA, respectively. After 8 weeks, it was seen that the amounts of OPN, BMP-2, RunX2 and ALP mRNA expression significantly decreased in 2.5% BN+10% HA, 2.5% BN, 5% BN+10% HA and 5% BN groups. It was shown that bone recovery was at the best grade in the groups, which contained 2.5% BN and 2.5% BN+10% HA when compared to the other groups. BN is a very promising agent that will be used in reconstructive surgery for the treatment of calvarial bone defects.

2.
Int J Pediatr Otorhinolaryngol ; 124: 106-110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176023

RESUMO

INTRODUCTION: That EGCG has strong antioxidant and anti-inflammatory activities as well as antibacterial activity against many streptococcus species suggests that it may be beneficial in the treatment of AOM. OBJECTIVE: Aim of the study is to reveal the molecular and biochemical effects of EGCG on LPS induced otitis media in rats. METHODS: Forty-two male albino Wistar rats were randomly divided into 7 groups. Inflammation was induced by administrating 50 µL of 1 mg/ml lipopolysaccharide (LPS). EGCG used 50 and 100 mg/kg/day and combined penicillin G (PENG) 48 h after LPS injection. RESULTS: The combined EGCG 50 and PENG group and the group with EGCG 50 alone showed the best anti-inflammatory effect on LPS-induced AOM. TNF-α and IL-1ß gene expression significantly down regulated EGCG 50 and combined with PENG compared to the otitis media group. The combination of PenG and EGCG 50 led to the best histopathological improvement. Both the inflammation and the membrane thickness of this group were at almost the same level as the healthy group and tympanum was seen normal. CONCLUSION: The results of this study make it clear that EGCG plays an important role in antioxidant and anti-inflammatory activity during AOM.

4.
Neurotoxicol Teratol ; 72: 22-28, 2019 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685503

RESUMO

Serotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-α) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 5-HT7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.

5.
Ear Nose Throat J ; 96(12): E14-E18, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29236276

RESUMO

Nasal polyposis (NP) is an inflammatory disease of the paranasal sinuses and nasal cavity. The primary purpose of our study is to determine the expression of 5-HT7 receptors both in nasal polyps and in healthy tissue in the nasal cavity. The subsequent aim is to compare the expression of 5-HT7 receptors in patients with NP and in inferior turbinate tissue (control). The study included 60 participants (40 with NP and 20 controls) aged 35 to 62 years. Nasal polyp samples were collected from all patients and relative 5-HT7 receptor expression analyses were performed. Reverse transcription polymerase chain reaction analysis of nasal polyps and control tissue identified 5-HT7 receptor expression in the nasal cavities of controls. This expression was approximately 67 times higher in nasal polyp tissue than in healthy tissue. Our study identifies the expression of 5-HT7 receptors in the nasal cavity for the first time and the first demonstration of increased 5-HT7 receptor expression in tissue from nasal polyps, which occur in the paranasal sinuses and nasal cavity.


Assuntos
Pólipos Nasais/metabolismo , Receptores de Serotonina/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/metabolismo , Mucosa Nasal/metabolismo , Seios Paranasais/metabolismo , Reação em Cadeia da Polimerase
6.
Braz. j. otorhinolaryngol. (Impr.) ; 83(6): 619-626, Nov.-Dec. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-889326

RESUMO

Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.


Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.

7.
Ren Fail ; 39(1): 314-322, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28100100

RESUMO

Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Meios de Contraste/efeitos adversos , Glicerol/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Catequina/farmacologia , Citocinas/sangue , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Chá
8.
Braz J Otorhinolaryngol ; 83(6): 619-626, 2017 Nov - Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27769794

RESUMO

INTRODUCTION: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. OBJECTIVE: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. METHODS: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. RESULTS: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. CONCLUSION: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.


Assuntos
Anlodipino/farmacologia , Anti-Inflamatórios/farmacologia , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Anlodipino/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Glutationa/análise , Glutationa/efeitos dos fármacos , Cobaias , Malondialdeído/análise , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Distribuição Aleatória , Valores de Referência , Reprodutibilidade dos Testes , Rinite/microbiologia , Rinite/patologia , Sinusite/microbiologia , Sinusite/patologia , Staphylococcus aureus , Superóxido Dismutase/análise , Superóxido Dismutase/efeitos dos fármacos , Resultado do Tratamento
9.
Eurasian J Med ; 48(2): 135-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27551178

RESUMO

After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future.

10.
Peptides ; 82: 35-43, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27208703

RESUMO

This study investigated possible role of U-II and its receptor expression in inflammation by using UTR agonist and antagonist in carrageenan induced acute inflammation. Rats were divided into 5 groups as (1) Healthy control, (2) Carrageenan control, (3) Carrageenan +Indomethacin 20mg/kg, orally, (4) Carrageenan +AC7954 (U-II receptor agonist, intraperitoneally) 30mg/kg and (5) Carrageenan +SB657510 (UTR antagonist, intraperitoneally) 30mg/kg. 1h after drug administration, carrageenan was injected. At the 3rd hour after carrageenan injection, agonist produced no effect while antagonist 63% anti-inflammatory effect respectively. UTR and UT-II expression increased in carrageenan induced paw tissue. Antagonist administration prevented the decrease in an antioxidant system and also capable to decrease TNF-α and IL-6 mRNA expressions. This study showed the role of urotensin II receptors in the physiopathogenesis of acute inflammatory response that underlying many diseases accompanied by inflammation.


Assuntos
Inflamação/tratamento farmacológico , Receptores Acoplados a Proteínas-G/metabolismo , Urotensinas/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Carragenina/toxicidade , Cromanos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Indometacina/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/genética , Ratos , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/genética , Fator de Necrose Tumoral alfa/genética , Urotensinas/genética
11.
Ostomy Wound Manage ; 62(3): 26-34, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26978857

RESUMO

Argan oil, produced from the kernels of the argan tree (Argania spinosa), has been shown to have antioxidant properties. To examine the effect of argan oil in second-degree burn wound healing, an in vivo experiment was conducted among 30 adult male Wistar rats divided into 5 equal groups: a sham group, a control group (burned but no topical agent), a group in which argan oil was applied once a day, a group in which argan oil was applied twice a day, and a group treated with 1% silver sulfadiazine once a day. Second-degree burns were created by scalding hot water (85˚ C for 15 seconds). Treatment began 24 hours after the burn injury; in the argan oil groups, 1 mL of argan oil was administered via syringe to the wound. The rate of wound healing was quantified by wound measurements on days 1, 7, and 14 after burn injury. Tissues were analyzed for molecular and histologic changes in TGF-ß expression and fibroblast activity. Percent contraction of burned skin tissue was determined using the stereo investigator program, which calculated the burn field to the millimeter. Means (SD) were calculated and compared using Duncan's multiple comparison test. The group receiving argan oil twice daily showed significantly increased mRNA levels of TGF-ß1 from 39.66- to 58.70-fold compared to the burn control group on day 14 (P less than 0.05). Both argan oil-treated groups showed significantly increased contraction compared to the burn control group at all 3 timepoints; the group receiving argan oil twice daily had a greater contraction rate (31% on day 7, 76% on day 14) than the silver sulfadiazine group (22% on day 7, 69% on day 14), (P less than 0.05). Histopathological assessments on days 3, 7, and 14 showed greater healing/contraction in both argan oil and silver sulfadiazine groups compared to the control group. These results suggest argan oil is effective in healing experimentally created second-degree burns in rats. Prospective, randomized, controlled clinical studies are needed to evaluate the safety, efficacy, and effectiveness of this treatment modality for patients with second-degree burn wounds.


Assuntos
Queimaduras/tratamento farmacológico , Fitoterapia , Óleos Vegetais/uso terapêutico , Cicatrização , Animais , Queimaduras/patologia , Masculino , Ratos , Ratos Wistar
12.
Basic Clin Pharmacol Toxicol ; 118(2): 150-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26176337

RESUMO

We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor-alpha (TNF-α) and IL-1ß and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre-treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre-treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti-inflammatory effects on high-dose PARA-induced hepatotoxicity in mice.


Assuntos
Acetaminofen/farmacologia , Doença Hepática Induzida por Substâncias e Drogas , Cromanos/farmacologia , Sulfonamidas/farmacologia , Urotensinas , Alanina Transaminase/sangue , Analgésicos não Entorpecentes/farmacologia , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos , Substâncias Protetoras/farmacologia , Resultado do Tratamento , Urotensinas/agonistas , Urotensinas/antagonistas & inibidores
13.
Respiration ; 90(2): 105-10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26088934

RESUMO

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) and obesity frequently occur together. The relationship between increased appetite and obesity is well known; however, despite existing knowledge about the relationship between OSAS and obesity, it is not fully understood. OBJECTIVES: This study aimed to evaluate the relationship between OSAS and the appetite-suppressing hormone nesfatin-1 independent of body mass index (BMI). METHODS: A total of 134 cases were included in the study; 102 with OSAS (OSAS group) and 32 healthy controls (control group). All cases underwent polysomnography, and nesfatin-1 levels were determined. RESULTS: Nesfatin-1 levels were significantly lower in the OSAS group compared to the control group (3,776.5 ± 204.8 and 4,056.2 ± 101.5 pg/ml, respectively; p < 0.001). In addition, there was a statistically significant negative correlation between nesfatin-1 and the apnea hypopnea index (r = -0.543; p < 0.001). The statistically significant relationship persisted after adjusting for confounding intergroup factors such as age, gender and BMI (p < 0.001). In the OSAS group, there was a statistically significant correlation between nesfatin-1 and neck circumference (r = -0.304; p = 0.02) but not between nesfatin-1 and BMI and waist circumference. There was no statistically significant difference in nesfatin-1 levels between the sexes. CONCLUSION: OSAS patients have lower nesfatin-1 levels compared to controls, and a greater nesfatin-1 deficit corresponds to an increased severity of OSAS and an increased neck circumference. Replacement therapy may be a potential treatment for obese OSAS patients who have lower nesfatin-1 levels, which may have additional benefits through appetite suppression and weight loss.


Assuntos
Tamanho Corporal , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a DNA/sangue , Pescoço , Proteínas do Tecido Nervoso/sangue , Obesidade , Apneia Obstrutiva do Sono , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/diagnóstico , Polissonografia/métodos , Índice de Gravidade de Doença , Fatores Sexuais , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Estatística como Assunto
14.
J Bone Miner Metab ; 33(5): 496-506, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25298328

RESUMO

The purpose of this study was to examine the effects bosentan (which is a strong vasoconstrictor) on bone fracture pathophysiology, and investigate the roles of the nonselective endothelin 1 receptor blocker bosentan on the bone fractures formed in rats through radiographic, histopathologic, and immunohistochemical methods. The rats were divided into three groups (six rats in each group): a femoral fracture control group, a femoral fracture plus bosentan at 50 mg/kg group, and a femoral fracture plus bosentan at 100 mg/kg group. The femoral fracture model was established by transversely cutting the femur at the midsection. After manual reduction, the fractured femur was fixed with intramedullary Kirschner wires. The radiographic healing scores of the bosentan 100 and 50 mg/kg groups were significantly better that those of the fracture control group. The fracture callus percent of new bone in the bosentan 100 mg/kg group was significantly greater than that in the control group. Also, semiquantitative analysis showed higher positive vascular endothelial growth factor and osteocalcin staining and lower positive endothelin receptor type A staining in the treatment groups than in the control group. Bosentan treatment also decreased tissue endothelin 1 expression relative to that in the fracture control group. As a result of our study, the protective effect of bosentan was shown in experimental femoral fracture healing in rats by radiographic, histopathologic, and molecular analyses.


Assuntos
Fraturas do Fêmur/tratamento farmacológico , Fêmur/efeitos dos fármacos , Consolidação da Fratura/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/metabolismo , Bosentana , Modelos Animais de Doenças , Fraturas do Fêmur/metabolismo , Fêmur/metabolismo , Masculino , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Basic Clin Pharmacol Toxicol ; 116(3): 236-43, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25200216

RESUMO

Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Antagonistas dos Receptores de Endotelina/farmacologia , Endotelina-1/metabolismo , Sulfonamidas/farmacologia , Animais , Antioxidantes/metabolismo , Bosentana , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Relação Dose-Resposta a Droga , Antagonistas dos Receptores de Endotelina/administração & dosagem , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Wistar , Estreptozocina , Sulfonamidas/administração & dosagem
16.
Neural Regen Res ; 9(10): 1020-4, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25206754

RESUMO

Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved significantly. These findings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.

17.
Invest Ophthalmol Vis Sci ; 55(6): 3517-24, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24833743

RESUMO

PURPOSE: We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 µg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS: The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS: Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.


Assuntos
Humor Aquoso/metabolismo , Endotelinas/genética , Regulação da Expressão Gênica , RNA/genética , Sulfonamidas/uso terapêutico , Uveíte/tratamento farmacológico , Animais , Bosentana , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Antagonistas dos Receptores de Endotelina , Endotelinas/biossíntese , Endotelinas/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Endotelina/biossíntese , Receptores de Endotelina/genética , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Uveíte/induzido quimicamente , Uveíte/metabolismo
18.
J Pharm Biomed Anal ; 97: 33-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24803031

RESUMO

A rapid, simple and sensitive UFLC-MS/MS method was developed and validated for the determination of bosentan in rat plasma using etodolac as an internal standard (IS) after liquid-liquid extraction with diethyl ether-chloroform (4:1, v/v). Bosentan and IS were detected using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions m/z 551.90→201.90 and 288.20→172.00, respectively. Chromatographic separation was performed on the inertsil ODS-4 column with a gradient mobile phase, which consisted of 0.1% acetic acid with 5mM ammonium acetate in water for solvent A and 5mM ammonium acetate in acetonitrile-methanol (50:50, v/v) for solvent B at a flow rate of 0.3mL/min. The method was sensitive with 0.5ng/mL as the lower limit of quantitation (LLOQ) and the standard calibration curve for bosentan was linear (r>0.997) over the studied concentration range (0.5-2000ng/mL). The proposed method was fully validated by determining specificity, linearity, LLOQ, precision and accuracy, recovery, matrix effect and stability. The validated method was successfully applied to plasma samples obtained from rats.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Antagonistas dos Receptores de Endotelina/sangue , Extração Líquido-Líquido/métodos , Sulfonamidas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Bosentana , Estabilidade de Medicamentos , Masculino , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Int J Neurosci ; 124(12): 935-43, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24617291

RESUMO

AIM: The present study aimed to demonstrate protective effects of alpha lipoic acid on experimental sciatic nerve crush injury model assessed with functional and electronmicroscopy analyses. METHODS: In this study, groups were; Group 1; sham operated, Group 2; applied only sciatic nerve crush (Control), Group 3; Sciatic nerve crush + treated ALA 25 mg/kg (received orally) and Group 4; Sciatic nerve crush + treated ALA 50 mg/kg. Subsequently, sciatic nerves crush injury induced by forceps. At the second and fourth week, all animals were evaluated for sciatic functional index (SFI) and histomorphometric analyses with electronmicroscopy. RESULTS: The SFI was significantly increased for both ALA-treated groups 30 days post-injury compared with control groups. The elecronmicroscopy results demonstrated that the axon diameter, the myelin diameter, the area of regenerating axon and miyelin were better in the treatment group than in the control group. Also ALA decreased IL-1ß and Caspase 3 levels that increased in SNC group. CONCLUSIONS: These results suggest that ALA neuroprotective agent for peripheral nerve injury (PNI) and promoted peripheral nerve regeneration via its anti-inflammatory and antiapoptotic effects.


Assuntos
Compressão Nervosa , Fármacos Neuroprotetores/farmacologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Ácido Tióctico/farmacologia , Animais , Feminino , Microscopia Eletrônica/métodos , Ratos , Ratos Wistar , Nervo Isquiático/metabolismo
20.
Eur J Pharmacol ; 726: 87-95, 2014 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-24462570

RESUMO

Paracetamol is one of the first rank drugs which cause hepatic damage during drug intoxications. Endothelin (ET) which is known as one of the most potent vasoactive agent has been shown to contribute in the pathophysiology of various diseases. We hypothesized that bosentan, which is a non-selective ET-1 receptor antagonist, can prevent liver damage. This study included 49 female rats. Groups; I: Healthy group, II: Paracetamol (2 g/kg orally). Groups 3, 4 and 5 received NAC 140 mg/kg (2 doses), BOS 45 mg/kg and BOS 90 mg/kg orally, respectively. 1 h after administration of pretreatment drugs, Groups 3, 4, 5 were given paracetamol. VI: received BOS 90 mg/kg. VII: received 140 mg/kg NAC (2 doses). According to biochemical results, TNF-α, ALT and AST levels were statistically increased in the paracetamol group, these parameters were improved in the bosentan groups. Paracetamol administration decreased SOD activity, GSH level and increased level of MDA in the liver, while bosentan administration significantly improved these parameters. In immunohistochemical staining ET-1 receptor expression was excessively increased in paracetamol group, but not in bosentan groups when compared to healthy control. All these results suggest that bosentan exerted protective effects against experimentally induced paracetamol toxicity in liver.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citoproteção/efeitos dos fármacos , Antagonistas dos Receptores de Endotelina/farmacologia , Fígado/efeitos dos fármacos , Receptores de Endotelina/metabolismo , Sulfonamidas/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/sangue , Bosentana , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Relação Dose-Resposta a Droga , Endotelina-1/metabolismo , Feminino , Fígado/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Fator de Necrose Tumoral alfa/sangue
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