• Title/Summary/Keyword: NOS model

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The Evaluation of Exogenous Melatonin Administration in Supraspinatus Overuse Tendinopathy in an Experimental Rat Model

  • Kocadal, Onur;Pepe, Murad;Akyurek, Nalan;Gunes, Zafer;Surer, Hatice;Aksahin, Ertugrul;Ogut, Betul;Aktekin, Cem Nuri
    • Clinics in Shoulder and Elbow
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    • v.22 no.2
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    • pp.79-86
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    • 2019
  • Background: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy. Methods: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically. Results: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (p<0.05). TOS, iNOS, VEGF, and OSI values after 3 weeks of triamcinolone administration, and TOS, VEGF, and OSI levels after 6 weeks of triamcinolone application, were significantly lower than the pre-treatment levels (p<0.05). Conclusions: Exogenous melatonin application in overuse tendinopathy reduces oxidative stress and inflammation. Melatonin might be an alternative potential molecule to corticosteroids in the treatment of chronic tendinopathy.

The effect of Panax notoginseng saponins on oxidative stress induced by PCV2 infection in immune cells: in vitro and in vivo studies

  • Wang, Qiu-Hua;Kuang, Na;Hu, Wen-yue;Yin, Dan;Wei, Ying-Yi;Hu, Ting-Jun
    • Journal of Veterinary Science
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    • v.21 no.4
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    • pp.61.1-61.16
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    • 2020
  • Background: Panax notoginseng saponins (PNS) are bioactive substances extracted from P. notoginseng that are widely used to treat cardiovascular and cerebrovascular diseases and interstitial diseases. PNS have the functions of scavenging free radicals, anti-inflammation, improving blood supply for tissue and so on. Objectives: The aim of this study was to investigate the effects of PNS on the oxidative stress of immune cells induced by porcine circovirus 2 (PCV2) infection in vitro and in vivo. Methods: Using an oxidative stress model of PCV2 infection in a porcine lung cell line (3D4/2 cells) and mice, the levels of nitric oxide (NO), reactive oxygen species (ROS), total glutathione (T-GSH), reduced glutathione (GSH), and oxidized glutathione (GSSG) and the activities of xanthine oxidase (XOD), myeloperoxidase (MPO) and inducible nitric oxide synthetase (iNOS) were determined to evaluate the regulatory effects of PNS on oxidative stress. Results: PNS treatment significantly reduced the levels of NO and ROS, the content of GSSG and the activities of XOD, MPO, and iNOS (p < 0.05), while significantly increasing GSH and the ratio of GSH/GSSG in infected 3D4/2 cells (p < 0.05).Similarly, in the in vivo study, PNS treatment significantly decreased the level of ROS in spleen lymphocytes of infected mice (p < 0.05), increased the levels of GSH and T-GSH (p < 0.05), significantly decreased the GSSG level (p < 0.05), and decreased the activities of XOD, MPO, and iNOS. Conclusions: PNS could regulate the oxidative stress of immune cells induced by PCV2 infection in vitro and in vivo.

An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model

  • Kwon, Jung Hyun;Kim, Kwan Chang;Cho, Min-Sun;Kim, Hae Soon;Sohn, Sejung;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.56 no.3
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    • pp.116-124
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    • 2013
  • Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

Semantic Network Analysis of Science Gifted Middle School Students' Understanding of Fact, Hypothesis, Theory, Law, and Scientificness (언어 네트워크 분석법을 통한 중학교 과학영재들의 사실, 가설, 이론, 법칙과 과학적인 것의 의미에 대한 인식 조사)

  • Lee, Jun-Ki;Ha, Minsu
    • Journal of The Korean Association For Science Education
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    • v.32 no.5
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    • pp.823-840
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    • 2012
  • The importance of teaching the nature of science (NOS) has been emphasized in the science curriculum, especially in the science curriculum for science-gifted students. Nevertheless, few studies concerning the structure and formation of students' mental model on NOS have been carried out. This study aimed to explore science-gifted students' understanding of 'fact', 'hypothesis', 'theory', 'law', and 'scientificness' by utilizing semantic network analysis. One hundred ten science-gifted middle school students who were selected by a national university participated in this study. We collected students' written responses of five items and analyzed them by the semantic network analysis(SNA) method. As a result, the core ideas of students' understanding of 'fact' were proof and reality, of 'hypothesis' were tentativeness and uncertainty, of 'theory' was proven hypothesis by experimentation, of 'law' were absoluteness and authority, and of 'scientificness' were factual evidence, verifiability, accurate and logical theoretical framework. The result of integrated semantic network illustrated that the viewpoint of science-gifted students were similar to absolutism and logical positivism (empiricism). Methodologically, this study showed that the semantic network analysis method was an useful tool for visualization of students' mental model of scientific conceptions including NOS.

Evaluation of Efficacy evaluation of Hwangryunhaedok-tang and Gungangbuja-tang on lipopolysaccharide (LPS)-induced inflammation mouse model (Lipopolysaccharide로 유도된 염증 mouse model에서의 황련해독탕(黃連解毒湯)과 건강부자탕(乾薑附子湯)의 효능평가)

  • Choi, You-Youn;Kim, Mi-Hye;Lee, Tae-Hee;Yang, Woong-Mo
    • Herbal Formula Science
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    • v.20 no.2
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    • pp.83-92
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    • 2012
  • Objectives : The aim of this study was to evaluate the efficacy of Hwangryunhaedok-tang (HHT) and Gungangbuja-tang (GBT) on lipopolysaccharide (LPS)-induced mouse model of inflammation. HHT and GBT are one of the representative prescriptions of cold drug and one of the representative prescriptions of hot drug, respectively. For experimental evaluation of their efficacy, we investigated the anti-inflammatory effects of HHT and GBT on LPS-induced inflammation and the mechanisms of their action. Methods : ICR mice were given a HHT (50, 500 mg/kg), GBT (100, 1000 mg/kg) extract orally on three consecutive days. On the third day, they were administered LPS intraperitoneally (35 mg/kg), 1 h after the last sample administration. Blood and liver samples were taken 6 h after the LPS challenge. Cytokine expression and inflammation-related protein factor analyses were performed by Western blotting. Results : Oral administration of HHT significantly reduced pro-inflammatory cytokines, including interleukin (IL)-6, and interferon (IFN)-${\gamma}$ in the serum. While GBT inhibited an increase of IL-6, IFN-${\gamma}$ was not affected. Immunoblot analysis showed that LPS-induced NF-${\kappa}b$ activation was inhibited by GBT, meanwhile HHT only inhibited NF-${\kappa}b$ expression at high does (500 mg/kg). In addition, HHT and GBT inhibited LPS-induced phosphorylation of Erk1/2, Jnk and p38 MAPKs. GBT also significantly inhibited i-Nos and Cox-2 expression, and HHT inhibited only i-Nos expression. Conclusions : Both of HHT and GBT showed anti-inflammatory effects against LPS-induced endotoxemia. However, HHT significantly decreased inflammatory cytokine levels, such as IL-6 and IFN-${\gamma}$ more than GBT, while GBT significantly inhibited inflammatory proteins, including NF-${\kappa}b$, MAP Kinases, i-Nos and Cox-2, more than HHT. These results suggest that HHT and GBT regulate the different mechanisms of action and pathways, presumably by regulating cytokine levels (IL-6, IFN-${\gamma}$), NF-${\kappa}b$ activation, and several pro-inflammatory gene expression, although both of HHT and GBT have anti-inflammatory effects.

The Neuroprotective Effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) Via Mediation of Nitric Oxide Synthase on Hypoxic-ischemic Brain Injury in Neonatal Rats

  • Jung, Ji-Eun;Keum, Kyung-Hae;Choi, Eun-Jin;Kim, Jin-Kyung;Chung, Hai-Lee;Kim, Woo-Taek
    • Neonatal Medicine
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    • v.18 no.1
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    • pp.59-69
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    • 2011
  • Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

Anti-angiogenic, Anti-inflammatory and Anti-nociceptive Activities of Vanillin in ICR Mice

  • Lim, Eun-Ju;Kang, Hyun-Jung;Jung, Hyun-Joo;Song, Yun-Seon;Lim, Chang-Jin;Park, Eun-Hee
    • Biomolecules & Therapeutics
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    • v.16 no.2
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    • pp.132-136
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    • 2008
  • The current study aimed to assess some novel pharmacological activities of vanillin. Vanillin inhibited the chick chorioallantoic membrane (CAM) angiogenesis. Vanillin had anti-inflammatory activity using the acetic acid-induced permeability model in mice. Anti-nociceptive activity of vanillin was shown using the acetic acid-induced writhing test in mice. Vanillin inhibited production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) but not cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Vanillin decreased the level of iNOS mRNA in the LPS-activated macrophages. Taken together, these results suggest that vanillin can have anti-angiogenic, anti-inflammatory and anti-nociceptive activities in ICR Mice.

Anti-inflammatory Effect of Dactyloquinone B and Cyclospongiaquinone-1 Mixture in RAW264.7 Macrophage and ICR Mice

  • Lee, Dong-Sung;Hwang, In Hyun;Im, Nam-Kyung;Jeong, Gil-Saeng;Na, MinKyun
    • Natural Product Sciences
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    • v.21 no.4
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    • pp.268-272
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    • 2015
  • Sesquiterpene-quinone is a class of secondary metabolites frequently encountered from marine sponge. The present study was designed to examine the anti-inflammatory action of sponge-derived dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture using lipopolysaccharide (LPS)-induced inflammatory responses. We measured the production of nitric oxide (NO), tumor necrosis factor-alpha ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), and interleukin-6 (IL-6) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 production, which increased by treatment with LPS, were significantly inhibited by DQB and CSQ1 mixture. It also decreased the production of NO production, and iNOS and COX-2 expression. Furthermore, it reduced 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice. These results demonstrate that sesquiterpene-quinone, DQB and CSQ1 mixture, might serve as a chemical pipeline for the development of anti-inflammatory agent.

Anti-atherosclerotic effect of herbal extracts in N(G)-nitro-L-arginine methyl ester-treated rats

  • Nagarajan, Senthil;Balamurugan, Rangachari;Shin, Eunju;Shim, Kyu-Suk;Kim, Min Jung;Lee, Jeong Jun;Lee, Jae Kwon
    • Journal of Applied Biological Chemistry
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    • v.62 no.3
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    • pp.265-273
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    • 2019
  • This study aimed to evaluate the anti-atherosclerotic and anti-hypertensive effects of six different plant extracts using a N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced rat model of hypertension. All extracts were administered orally for six weeks. At the end of the study period blood pressure, blood flow, aortic histopathology, and hepatic endothelial nitric oxide synthase (eNOS) expression were measured. Subsequently, we also measured the levels of intracellular reactive oxygen species, nitric oxide (NO), and anti-inflammatory cytokines in vitro. Based on these screening results, we selected extracts of Cinnamomum cassia (C. cassia) and Salvia miltiorrhiza (S. miltiorrhiza) for further evaluation. C. cassia and S. miltiorrhiza extracts ameliorated hypertension and atherosclerosis in L-NAME-treated rats in a dose-dependent manner. In addition, a mixture of C. cassia and S. miltiorrhiza had an additive effect to reduce blood pressure, increase blood flow, and normalize aortic tissue. This mixture demonstrated anti-oxidative and anti-inflammatory activities in vitro. In conclusion, although further analysis of the therapeutic mechanism is required, the anti-hypertensive and anti-atherosclerotic effects of this mixture are likely mediated by increased eNOS expression, and its anti-oxidative and anti-inflammatory activities.

Astaxanthin Ameliorates Atopic Dermatitis by Inhibiting the Expression of Signal Molecule NF-kB and Inflammatory Genes in Mice

  • Donghwan, Kim;Yong-Suk, Kim;Ho Sueb, Song
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.304-309
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    • 2022
  • Background: This study was conducted to determine the anti-inflammatory effect of astaxanthin, on atopic dermatitis. Methods: Changes in mouse body weight, lymph node weight, and the degree of improvement in symptoms were measured to determine the inflammatory response. Real-time reverse transcription-polymerase chain reaction tests were performed to determine the degree of expression of inflammation-related cytokines (IL-31 and IL-33 and chemokines such as CCL17 and CCL22), and western blot analysis was performed to evaluate the expression of inflammation-related factors (iNOS, COX-2, and NF-kB signaling molecules p-IkBα, p50, p-65 and pSTAT3). Results: The degree of symptoms significantly improved in the PA+AX group. Lymph node weight in the PA+AX group was lower than the PA group. Inflammatory cytokines (IL-31, IL-33, and inflammatory chemokines such as CCL17 and CCL22) were significantly reduced in the PA+AX group compared with the PA group. The expression of inflammatory genes (iNOS, COX-2, NF-kB and signaling molecules (p-IkBα, p50, p65, and p-STAT 3) was lower in the PA+AX group compared with the PA group. Conclusion: Astaxanthin may modulate the inflammatory response in a mouse model of atopic dermatitis and has an anti-inflammatory effect.