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1.
Inflammopharmacology ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504222

RESUMO

AIM: This study aimed to demonstrate the role of serotonin 7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. MATERIAL AND METHOD: Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. RESULTS: We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. CONCLUSION: The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.

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.


Assuntos
Antioxidantes/uso terapêutico , Catequina/análogos & derivados , Otite Média/tratamento farmacológico , Animais , Antibacterianos/uso terapêutico , Antioxidantes/farmacologia , Catequina/farmacologia , Catequina/uso terapêutico , Regulação para Baixo , Quimioterapia Combinada , Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Lipopolissacarídeos , Masculino , Otite Média/induzido quimicamente , Otite Média/patologia , Penicilina G/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Membrana Timpânica/patologia
4.
Eurasian J Med ; 51(1): 75-79, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30911262

RESUMO

Objective: The aim of the present study was to demonstrate the effects of misoprostol in ovalbumin-induced allergic rhinitis (AR). The second purpose was to compare the effect profile of the combination of an antihistamine with misoprostol during treatment of AR. Materials and Methods: Twenty-five adult male rats were used and were randomly classified into five groups (n=5): healthy+saline, AR, AR and desloratadine (D)-treated group, AR and misoprostol (M)-treated group, and AR and combined-treated group. Results: Desloratadine administration had significantly lower nasal symptoms than the AR group, but nasal symptoms in the AR+M group were better than those in the AR+D group. The best improvement in serum IgE levels was seen in the misoprostol alone and combination treatment groups. Conclusion: We suggest that prostaglandins should be considered in the treatment of AR, and that the effects of these types of drugs should be tested clinically in patients.

5.
Clin Psychopharmacol Neurosci ; 17(2): 211-221, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-30905121

RESUMO

Objective: This study investigated changes in urotensin-II (U-II) and endocan levels which can be used as an early biological marker of endothelial injury in the episode and remission phases of bipolar affective disorder (BAD). Methods: We compared endocan and U-II levels, which has been shown to be closely associated with neurotransmitter systems in addition to continuity of endothelial structure and inflammatory response, in patients with BAD in remission for at least one year (n=42) and in patients still in manic or depressive episodes (n=16) with healthy controls (n=30). Results: Both endocan and U-II levels were significantly higher in the bipolar patients than in the controls. Endocan and U-II levels were also significantly correlated with one another (p =0.000, r=0.833). Both endocan (p =0.000) and U-II levels (p =0.000) were significantly higher in the bipolar attack group compared to the subjects in remission, and in the remission group compared to the controls. Conclusion: In this study we determined significantly higher endocan and U-II levels in BAD compared to the controls, while serum endocan and U-II levels of patients undergoing attacks were also significantly higher than those of the controls and also those of patients in remission.

6.
Life Sci ; 221: 327-334, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30797018

RESUMO

AIMS: Sepsis is a complex pathophysiological event involving systemic inflammatory response syndrome, multiple organ dysfunction syndrome and tissue damage such as acute lung injury (ALI). Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Antioxidant, antibacterial and antiinflammatory effects of gossypin (GOS)-like flavonoids have been shown and we have hypothesized that GOS have roles in sepsis induced inflammation of lungs. MAIN METHODS: Cecal ligation and puncture (CLP) induced sepsis model was induced in rats. Effects of GOS on oxidative stress, histopathology, nuclear factor kappa B (NF-κB), IL-6 positivity and NLRP3, HMGß1, TNF-α, NF-κB, IL-1ß mRNA expression levels were evaluated in lung tissues of the septic rats. KEY FINDINGS: GOS 20 (20 mg/kg) administration to septic rats decreased oxidative stress and supported antioxidant system in lungs. GOS administration also decreased the tissue NF-κB and IL-6 immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. HMGß1, NLRP3, NF-κB, IL-1ß, and TNF-α mRNA expression significantly increased in the CLP group. Both doses of GOS significantly reduced these mRNA expression as compared with the levels in the CLP group demonstrating its anti-inflammatory potential. SIGNIFICANCE: GOS administration, may represent a novel treatment for the prevention of lung damage occurred after sepsis induction. This effect of GOS might be related to its anti-inflammatory potential that result in decreased cytokine response and improved oxidative status.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Flavonoides/farmacologia , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Animais , Antioxidantes , Citocinas , Modelos Animais de Doenças , Feminino , Flavonoides/metabolismo , Proteínas HMGB , Inflamação , Interleucina-1beta , Interleucina-6 , Pulmão/citologia , Pulmão/fisiologia , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Ratos , Ratos Wistar , Sepse/induzido quimicamente , Sepse/fisiopatologia , Fator de Necrose Tumoral alfa
7.
Naunyn Schmiedebergs Arch Pharmacol ; 392(2): 135-145, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353214

RESUMO

Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1ß, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1ß, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.


Assuntos
Lesão Pulmonar Aguda/genética , Receptores Acoplados a Proteínas-G/genética , Sepse/genética , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Ceco/cirurgia , Citocinas/genética , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Ligadura , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/genética , Fragmentos de Peptídeos/farmacologia , Quinolinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/patologia , Superóxido Dismutase/metabolismo , Ureia/análogos & derivados , Ureia/farmacologia , Urotensinas/farmacologia
8.
Eur J Pharmacol ; 818: 457-469, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29133126

RESUMO

This study aimed to investigate the potential role of urotensin-II receptors in sepsis-induced lung injury in diabetic mice using urotensin-II receptor agonists and antagonists. A total of 110 male CD1 mice were used in this study. Diabetes was induced by 200mg/kg streptozotocin. One month after diabetes induction, the cecal ligation and puncture-induced polymicrobial sepsis model was applied in the diabetic and non-diabetic mice. Low and high doses of human urotensin-II agonist (HU-II) and antagonist (palosuran) were administered one hour after sepsis induction. HU-II administration was repeated in two-hour intervals. Blood and tissue samples were collected at 6 and 12H after sepsis induction for biochemical, molecular, and histopathologic examinations. Regarding to the lungs mRNA expression and immunohistochemistry results of TNF-α, IL1 ß, IL6, and NF-κB, it was observed that cytokine levels significantly increased in the diabetes group and the sepsis groups compared to the healthy group; this increase was significantly higher in the diabetes-sepsis groups. Our biochemical (superoxide dismutase, glutathione, and malondialdehyde) and histopathological findings in the lungs also supported these results. All increased parameters were significantly reduced dose-dependently by the administration of palosuran, an urotensin receptor antagonist. mRNA expression of urotensin-II and its receptor were examined in the lung tissue. Palosuran administration significantly reduced the urotensin-II and urotensin-II receptor levels that increased in the damaged tissue. This study has shown that urotensin-II and urotensin-II receptors contribute to the aggravation of sepsis-induced lung injury in diabetic mice; palosuran prevents this damage by antagonizing urotensin-II receptors.


Assuntos
Diabetes Mellitus Experimental/complicações , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Sepse/complicações , Urotensinas/metabolismo , Animais , Peso Corporal , Jejum/sangue , Regulação da Expressão Gênica , Interleucina-6/genética , Lesão Pulmonar/genética , Masculino , Camundongos , NF-kappa B/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/genética , Fator de Necrose Tumoral alfa/genética , Urotensinas/genética
9.
Acta Odontol Scand ; 76(2): 130-134, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29057714

RESUMO

BACKGROUND: Radiotherapy is a commonly used treatment modality in head and neck cancer; however, it also negatively affects healthy structures. Direct damage to oral soft and hard tissue frequently occurs with radiotherapy. In this study, we aimed to evaluate the effect of radiotherapy on bone surrounding titanium dental implants via biomechanical and molecular methods. MATERIALS AND METHODS: Fifty-four implants were inserted in the left tibiae of 18 adult male New Zealand rabbits (3 implants in each rabbit). After 4 weeks of the implant surgery, the left tibiae of 12 rabbits were subjected to a single dose of irradiation (15 Gy or 30 Gy). Four weeks after the irradiation, rabbits were sacrificed and removal torque test was done for the biomechanical evaluation. Bone morphogenetic protein-2 (Bmp-2) and fibroblast growth factor-2 (Fgf-2) expression analyses were performed with Real-time PCR. Statistical analysis was done using SPSS. RESULTS: The control group showed significantly higher removal torque value than the 15 and 30 Gy irradiation groups, and the 15 Gy irradiation group had higher removal torque value than the 30 Gy irradiation group (p < .001). The 15 Gy and 30 Gy irradiation groups had significantly lower Bmp-2 and Fgf-2 mRNA expressions than the control group (p < .001). In addition, the 30 Gy irradiation group had significantly lower Bmp-2 (p < .01) and Fgf-2 mRNA expressions (p < .001) than the 15 Gy group. CONCLUSION: Radiotherapy with 15 and 30 Gy doses can adversely affect osseointegration of implants by reducing the quality of bone and impairing the bone-to-implant contact. The mechanism of action seems to be related to alterations in Bmp-2 and Fgf-2 mRNA expressions.


Assuntos
Proteína Morfogenética Óssea 2/efeitos da radiação , Implantes Dentários , Materiais Dentários/efeitos da radiação , Titânio/química , Animais , Materiais Dentários/química , Relação Dose-Resposta à Radiação , Masculino , Osseointegração/efeitos da radiação , Coelhos , Propriedades de Superfície , Torque
10.
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
11.
Iran J Basic Med Sci ; 19(5): 483-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27403254

RESUMO

OBJECTIVES: In the present study, our aim was to investigate the possible protective effects of epigallocatechin gallate (EGCG) on lipopolysaccharide (LPS)-induced hepatotoxicity by using Hep3B human hepatoma cells. Specifically, the study examines the role of some proinflammatory markers and oxidative damage as possible mechanisms of LPS-associated cytotoxicity. Consequently, the hepatocellular carcinoma cell line Hep3B was chosen as a model for investigation of LPS toxicity and the effect of EGCG on LPS-exposed cells. MATERIALS AND METHODS: The Hep3B human hepatoma cells were used for this study. The cytotoxic effects of chemicals (EGCG and LPS), AST and ALT levels, SOD and CAT activities, GSH-Px level and TNF-alpha and IL-6 levels were detected by using different biochemical and molecular methods. LPS and EGCG were applied to cells at various times and doses. RESULTS: The highest treatment dose of EGCG (400 µM) led to a dramatic decrease in SOD level and increase in CAT and GSH levels. Additionally, the highest dose of EGCG also led to a dramatic increase in TNF-alpha and IL-6 levels. On the other hand, effective doses of EGCG (200 and 100 µM) normalized all related parameters levels. CONCLUSION: LPS caused hepatotoxicity, but interestingly, a high dose of EGCG was found to be a cytotoxic agent in this study. However, other two doses of EGCG led to a decrease in both inflammatory cytokine levels and antioxidant enzyme levels. Further studies should examine the effect of EGCG on secondary cellular signaling pathways.

12.
Pharmacol Rep ; 64(3): 594-602, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22814013

RESUMO

BACKGROUND: Cisplatin is a platinum derivative frequently used in the chemotherapy of different solid tumors. This biochemical and histologic study investigated a possible protective effect of mirtazapine with regard to cisplatin-induced nephrotoxicity in the rat. METHODS: The animals were divided into 4 groups: 15 mg/kg mirtazapine + 10 mg/kg cisplatin, 30 mg/kg mirtazapine + 10 mg/kg cisplatin, only 10 mg/kg cisplatin and negative control (healthy) group. During 14 days, the treatment and treated control group took drugs, while the healthy animals were given distilled water on the same schedule. All animals were sacrificed by high-dose anesthesia at the end of the 14 days of treatment; their kidneys were removed and subjected to histologic and biochemical study. RESULTS: In both of the doses we used, mirtazapine decreased the levels of malondialdehyde, creatinine, blood urea nitrogen and myeloperoxidase activity when compared to cisplatin group. On the other hand, it increased total glutathione level in all doses. Slight histopathological findings were determined in mirtazapine groups when compared to cisplatin control group. CONCLUSION: In the light of our results and literature knowledge, we can conclude that the protective effect of mirtazapine in cisplatin toxicity originates from its own antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Cisplatino/toxicidade , Nefropatias/prevenção & controle , Mianserina/análogos & derivados , Animais , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/farmacologia , Antineoplásicos/toxicidade , Antioxidantes/administração & dosagem , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Nefropatias/induzido quimicamente , Masculino , Malondialdeído/metabolismo , Mianserina/administração & dosagem , Mianserina/farmacologia , Mirtazapina , Peroxidase/metabolismo , Ratos , Ratos Wistar
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