• 약학회지
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• 제43권2호
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• pp.198-207
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• 1999

The aim of the present investigation was to examine whether YH439, a hepatoprotective agent, exerts protective effect against hepatotoxicity and reduces the production of cytokines and NO in lipopolysaccharide (LPS)-primed rats with carbon tetrachloride ($CCl_4$). Administration of LPS following a single dose of CCl4 injection resulted in remarkable elevations of the serum $TNF{\alpha},{\;}IL-l{\beta$ and IL-6 level. The serum NO level was moderately elevated and severe liver damage was evidenced by increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities. YH439 decreased the levels of TNF, $IL-l{\beta}$, IL-6, ALT, SDH as well as NO in the serum elevated by CCl4+LPS in a dose-dependent manner. Inducible nitric oxide synthase (iNOS) level was decreased in the liver of rats treated with YH439. The increased iNOS activity induced by LPS and $interferon-{\gamma}$ was significantly decreased in RAW 264.7 cells by YH439 treatment. YH439 increased the GSH level decreased by $CCl_4+LPS$ and suppressed the ratio of GSSG/GSH. The reduction of hepatotoxicity by YH439 may associated with the decrease in the production of cytokines as well as suppression of iNOS protein in conjunction with an increase in the GSH level.

• Asian-Australasian Journal of Animal Sciences
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• 제22권7호
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• pp.1048-1053
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• 2009

The present study was conducted to determine the effects of chitosan on nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity in serum, and relative expression of iNOS mRNA in the duodenum, jejunum, and ileum of broiler chickens. A total of 240 one-day-old Arbor Acre mixed-sex broiler chickens were randomly allotted to six dietary treatments with five replicates in each treatment and eight chickens in each replicate. The broiler chickens in the six treatments were fed the basal diet supplemented with 0 (control), 0.05, 0.2, 0.5, 1.0 or 2.0 g/kg chitosan. The trial lasted for 42 days. The results showed that dietary chitosan enhanced NO content and iNOS activity in serum as well as iNOS mRNA expression in the duodenum and ileum of broiler chickens in a quadratic dose-dependent manner (p<0.05), and improved jejunum iNOS mRNA expression in a quadratic dose-dependent manner (p<0.10) with increasing addition of chitosan. Chicks fed a diet containing 0.5-1.0 g/kg chitosan had higher NO content and iNOS activity in serum as well as small-intestinal iNOS mRNA expression compared with birds given the control diet, but positive effects of chitosan tended to be suppressed when addition of chitosan in the diet was increased to 2.0 g/kg. These results implied that there was a threshold level of chitosan inclusion beyond which progressive reductions in serum NO content and small intestinal iNOS expression occured, and the regulation of chitosan on immune functions in chickens is probably associated with activated expression of iNOS and NO secretion.

• 대한물리치료과학회지
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• 제9권4호
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• pp.45-52
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• 2002

Rats that are fed a fructose-rich diet develop hypertension, insulin resistance, and hypertriglyceridemia. To elucidate whether altered expression levels of endothelin-1 and nitric oxide synthase are related to the development of insulin-resistant hypertension, we examined the present study. Male Sprague-Dawley rats were fed a fructose-rich diet for 5 weeks. Systolic blood pressure significantly increased in fructose-fed rats. While serum free fatty acid and plasma nitrite/nitrate levels did not significantly differ between the fructose-fed and control groups, plasma insulin and serum triglyceride concentrations significantly increased in the former. Endothelin-1 mRNA expression in the aorta increased in fructose-fed rats. Neither the protein expression of constitutive nitric oxide synthase nor that of inducible nitric oxide synthase were significantly affected by fructose feeding. However, nitrite/nitrate levels in the aorta were significantly increased. These results suggest that an increase in vascular endothelin-1 is an important contributing factor to the development of hypertension in fructose-fed rats. However, the vascular nitric oxide pathway may not be causally related to the development of fructose-induced hypertension.

• 생명과학회지
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• 제9권2호
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• pp.201-206
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• 1999

본 연구는 정상 및 호흡곤란 신생아의 혈청내에 존재하는 nitric oxide(NO)의 생성을 관찰하고 erythropoietin (EPO)의 생성을 보기 위하여 정상 신생아 18명과 호흡곤란 신생아 16명으로부터 혈액을 채취하여 혈청내에서의 NO 및 EPO 생성량을 enzyme-linked immunosorbant assay법으로 측정하여 다음과 같은 결과를 얻었다. 1. 정상신생아의 혈청내 nitrite ion은 14.9$\pm$3.2 $\mu$M을 나타냈고 호흡곤란신생아군에서는 12.8$\pm$3.3 $\mu$M을 나타냄으로서 정상 대조군보다 호흡곤란군이 NO생성량이 낮음을 알 수 있었다. 2. 정상신생아의 혈청내 EPO는 16.2$\pm$3.4 mU/ml을 나타냈고 호흡곤란신생아군에서는 21.2 $\pm$5.4 mU/ml을 나타냄으로서 정상 대조군보다 호흡곤란군이 EPO생성량이 많음을 알 수 있었으며 통계학적으로 매우 유의한 차이를 나타냈다. 이상의 결과에서 호흡곤란증후군에서는 정상대조군에 비하여 NO생성이 대체적으로 저하되어 있음을 알 수 있었고 반대로 EPO의 생성은 증가되어 나타남으로서 EPO 상승에 따른 임상증상도 발현될 가능성이 있다하겠다.

• 운동영양학회지
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• 제14권2호
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• pp.95-101
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• 2010

The purpose of this study was to evaluate changes of body composition, cardio-respiratory function in ventilation threshold (VT) and maximal state exercise, systolic (SBP) and diastolic blood pressure (DBP) and serum nitric oxide (NO) production during acute reducing salt (RS) supplementation in college elite athletes. Variables of cardio-respiratory function during rest, ventilation threshold and maximal exercise was not shown a significantly difference between RS supplementation and non-supplementation, there was shown a significant increase in ventilation threshold time (p<0.05) and exhaustion time (p<0.05) during RS supplement compared to non-supplement. SBP and DBP were not shown a significant difference between RS supplement and non-supplement. This result suggests that acute intake of RS is not increased a blood pressure. Serum NO production was not significant difference in the RS supplement group, but it was shown a significantly increased levels (p<0.01, vs. recovery 30 min.) immediately after maximal exercise in the non-supplement group. This result suggests that acute intake of RS have important role in inhibition of serum NO production during maximal exercise. Conclusively, This study suggest that acute intake of RS was not influence in body composition variables, but it was positive effect in ventilation threshold time, exhaustion time, maintenance of blood pressure and inhibition of serum NO production in maximal treadmill exercise.

• Journal of Trauma and Injury
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• 제21권1호
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• pp.59-65
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• 2008

Purpose: The aim of this study was to evaluate the effect of overexpression of heat shock protein 70 (HSP70) on the expression of inducible nitric oxide synthase and on the concentration of nitric oxide and to determine the mechanism for the relationship between HSP70 and inducible nitric oxide synthase (iNOS) in sepsis. Methods: Experiments were performed on male Sprague-Dawley rats, and sepsis was induced by using cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 h after initiation of sepsis. We acquired serum and lung tissues from the rats 12 h or 24 h after initiation of sepsis. We analyzed the concentration of nitric oxide, the expression of HSP70 in the lung, and the gene expression of iNOS in the lung. Results: In CLP+GLN, glutamine given after initiation of sepsis enhanced the expression of HSP70 in the lung at 12 h (CLP+GLN vs. CLP:: $47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, p = 0.025) and 24 h (CLP+GLN vs. CLP: $47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, p = 0.004). In CLP+GLN, glutamine attenuated the expression of iNOS mRNA in the lung at 12 h (CLP+GLN vs. CLP: $4167.17{\pm}951.59$ vs. $5513.73{\pm}1051.60$, p = 0.025) and 24 h (CLP+GLN vs. CLP: $9,437.65{\pm}2,521.07$ vs. $18,740.27{\pm}8,241.20$, p = 0.016) and reduced the concentration of nitric oxide in serum at 12 h (CLP+GLN vs. CLP: $0.86{\pm}0.48$ vs. $3.82{\pm}2.53{\mu}mol/L$, p = 0.016) and 24 h (CLP+GLN vs. CLP: $0.39{\pm}0.25$ vs. $1.85{\pm}1.70{\mu}mol/L$, p = 0.025). Conclusion: The overexpression of HSP70 induced by the administration of glutamine in sepsis attenuated the gene expression of iNOS and reduced the concentration of nitric oxide.

• 대한의생명과학회지
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• 제5권1호
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• pp.85-93
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• 1999

마우스 간 세포주인 BNL CL.2의 시험관내 배양에서 혈청과 IFN-$\gamma$가 세포주의 nitric oxide (NO)생성과 세포 손상에 미치는 영향을 알아보기 위한 실험을 하였다. 혈청이 공급된 배양에서 IFN-$\gamma$에 의한 세포 생존율은 거의 변동이 없었으나, 혈청을 제거한 배양에서는 약 65%의 생존율이 유지되었으며, NO생성 억제제인 N$^{G}$-monomethy-L-arginine (NMA)의 첨가는 농도 의존적으로 세포의 생존율을 감소시켰다. 혈청이 제거된 BNL CL.2 세포주는 IFN-$\gamma$ 단독 처리에서도 NO를 생성할수 있었으며, IFN-$\gamma$와 lipopolysaccharide (LPS)의 복합 처리는 세포주의 NO 생성을 상승적으로 증가시 켰다. 또한 protein tyrosine kinase (PTK) inhibitor인 herbimycin A와 genistein에 의해서 NO 생성이 억제되어 PTK의 활성이 혈청이 고갈된 BNL CL.2세포에서 NO의 생성에 중요한 역할을 담당하고 있기 때문으로 판단된다. IFN-$\gamma$의 독성은 혈청을 제거시킬 때 NO 생성 억제제에 상승적으로 간세포를 손상시키며, 이때 NO가 IFN-$\gamma$에 의해 유도된 손상을 어느 정도 억제시키는 것을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.515-521
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• 1997

Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

• Archives of Pharmacal Research
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• 제20권3호
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• pp.239-246
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• 1997

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/ nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that $N^{G}$-monomethyl-L-arginine (MMA) and $ N^{G}, N^{G}$-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.

• Journal of Preventive Medicine and Public Health
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• 제31권2호
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• pp.265-274
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• 1998

To investigate the change of nitric oxide(NO), copper, and zinc in serum on smoking and alcohol ingestion in young adults, this study was performed in a cross-sectional study in 127 healthy men in Korea who had HBsAg(-), HCVAb(-), and no symptomatic liver, heart, gastrointestinal, chronic diseases, and inflammatory sign(lower than 10,000 white blood cell count in CBC). At the men's entry into the study, blood samples were drawn from each subject and immediately centrifuged for analysis of NO, copper, and zinc. Each man completed a questionnaire that provided information on smoking, alcohol intake and present and past medical history NO was analyzed by HPLC(Green et al., 1982), copper and zinc by atomic absorption spectrophotometer with air-acetylene flame and total cholesterol(TC) by Spectrum EPX. Smoking(number of cigarettes per day and pack-year) and alcohol intake was grouped fertile. Copper was adjusted for age and zinc and for age and TC. NO, copper, and zinc on smoking and alcohol ingestion were analyzed in general linear models, respectively. NO, copper and zinc in serum did not show statistical differences between non-smoking and high-smoking group and no-alcohol intake and high-alcohol intake group. This study suggested that copper, zinc, and NO was not. good biological marker for early effect by smoking and alcohol intake in young adults. However, selection bias should be considered in evaluation of this result. A large prospective study will be needed in advance on usefulness of copper, zinc, and NO as a marker for risk factors and early change of atherosclerosis.