• 대한약리학회지
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• 제32권2호
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• pp.211-219
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• 1996

The inhibitory effect of cyclosporin A (CsA) on nitric oxide production is not related to the immunosuppressive action of the drug, but to the renal toxicity and arterial hyper-tension. In this study the experimental interventions to reverse the inhibition of nitric oxide production by cyclosporin A in rat aortic smooth muscle cells were examined. CsA inhibited the accumulation of nitrite, the stable end product of nitric oxide, in culture media in a concentration $(0.1{\sim}100{\mu}g/ml)-dependent$ manner. The inhibitory effect of CsA on nitrite accumulation were not antagonized by arginine (10 mM), a substrate of nitric oxide synthase, nor by calcium ionophore A23187 $(7{\mu}M)$. Forskolin, an activator of adenylate cyclase, which enhanced iNOS induction at transcriptional level, completely reversed the inhibitory action of CsA on nitrite accumulation. However, PMA (2 nM) and PDB (50 nM), PKC activators, increased the inhibitory action of CsA on nitrite accumulalion. From these results, it is suggested that cyclic AMP-elevating agents may be candidates of therapeutic agents in prevention and treatment of renal toxicity and arterial hypertension induced by CsA. Among conventional antihypertensive drugs, calcium channel blockers and ${\alpha}-blockers$ are preferred to ${\beta}-blockers$.

• 한국발생생물학회지:발생과생식
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• 제1권2호
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• pp.157-164
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• 1997

To study the regulation of porcine follicular cell apostosis by gonadotropin, steroid, and nitric oxide, we analyzed DNA fragmentation, the hallmark of apoptosis, and nitrite production of porcine granulosa cells. Dissected indiidual follicles from ovary were separated in size (small, 2-3 mm; medium, 5-6 mm; large, 7-8 mm) and isolated granulosa cells were classified morpholocally as atretic or nonatretic. Nitrite concentration was measured by mixing follicular fluids with an equal volume of Griess reagent. Follicular nitric oxide (NO) concentration of healthy follicles was higher than that of atretic follicles. Apoptotic DNA fragmentation was suppressed in non-apoptotic granulosa cells. Follicular apoptosis was induced by androgen but prevented by gonadotropin in vitro. Apoptosis was confined to the granulosa cells. But it was not clear whether apoptosis of granulosa cells were isolated, incubated with or without gonadotropin, androgen and sodium nitroprusside (SNP), respectively at $37^{\circ}C$ for 24 hrs. Cultured granulosa cells were used to extract genomic DNA and culture media was asssayed for nitrite concentration. Nitrite production of culture media was increased, while apoptotic DNA fragmentation was suppressed in PMSG, hCG, testosterone+SNP and SNP treated groups. Nitrite concentration in culture media was decreased, but apoptotic DNA fragmentation was induced in testosterone treated group. These data suggest that NO production and apoptosis may be involved of granulosa cell apoptosis induced by testosterone.

• 약학회지
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• 제43권2호
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• pp.214-220
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• 1999

Present study was aimed to examine whether indomethacin affected the production of NO in the rat paw exudate by carrageenin. Paw edema and nitrite/nitrate levels in the paw exudate were maximal after 4 h and remained elevated up to 10 h, whereas indomethacin (10 mg/kg, po) significantly inhibited the carrageenin-induced paw edema and levels of nitrate in the paw exudate. However, paw edema and nitrite/nitrite levels were increased thereafter for 10 h. Indomethacin also enhanced the expression of iNOS mRNA and protein 4 h after carrageenin infection. Indomethacin inhibited the level of $PGE_2$ in the paw exudate in a time-dependent manner. These results suggest the possibility that indomethacin may potentiate expression of iNOS and subsequently increase nitrite/nitrate level in the late phase of carrageenin-induced rat paw inflammation possibly by suppressing cycloxygenase activity.

• 한국식품영양학회지
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• 제34권3호
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• pp.295-301
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• 2021

Steaming is a method that has traditionally been used for medicinal plant extraction. This study investigated nitrite oxide production, ferrous ion chelating activity, α-glucosidase, xanthine oxidase, and acetylcholinesterase inhibitory activities of ethanol, acetone and hot-water extracts of Codonopsis lanceolata prepared by steaming seven times. MTT assay showed that each extract was non-toxic up to a concentration of 700 ㎍/mL confirming that there was no cytotoxicity in all extracts. The α-glucosidase, xanthine oxidase, and acetylcholinesterase inhibitory activities exhibited by the hot-water extract obtained from steaming seven times were higher (83.1%) than the other extracts. Higher production of nitrite oxide and better ferrous chelating activity was recorded with hot-water extract compared to ethanol and acetone extracts. These results indicated that more steaming of Codonopsis lanceolata extracts would be required to validate the possibility of developing antioxidants. Also, further study is needed to determine if the components present in the tested extracts might be useful in the prevention of Alzheimer's disease. These results showed that hot-water extracts may be useful for their antioxidant and the production inhibitory activity of nitrite oxide. It will be helpful in the investigation of the constituent analysis of the steam-processed product of Codonopsis lanceolata.

• 대한한의학회지
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• 제19권2호
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• pp.112-124
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• 1998

The purpose of this study was to investigate the effect of Brousson etiae fructus (BF) on the urethral nitrite level and the urethral nitric oxide synthase (NOS) activity in streptozotocin (STZ) induced diabetic rats. In vitro, the urethral NOS activity was not noted in the level of Dose of extract prepared from BF. In vivo, the urethral NOS activity was increased in normal rats and STZ induced diabetic rats by dose and term of extract prerared from BF. The the NOS activity decreased in STZ induced diabetic rats was increased as highly as norma1 group by the extract of BF The level of urethral nitrite and glutathione was increased too. But the level of urethral lipid peroxide increased in STZ induced diabetic rats was decreased as lowly as normal group by the extract of BF. In conclusion, the extract of BF can restore erectile dysfunction of STZ induced diabetic rats.

• 생명과학회지
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• 제5권1호
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• pp.20-25
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• 1995

기생충감영시 cytokine으로 활성화된 대식세포가 방어기전의 Effector cell로 작용할 때 분비하는 nitric oxide의 양 및 TNF-$\alpha$ 와 IFN-$\gamma$의 분비정도와 nitric oxide와의 상관관계 등을 알아보기 위하여 3종의 흡충류, Fasciola, paragonimus, Schistosma의 조항원 (100mg/ml)을 마우스 복강내에 주사　 후 24시간, 72시간, 9일간격으로 마우스의 대식세포(1X10$^{6}$/ml)를 분리하여 RPMI 배지 (10% FCS 첨가)에서 48시간 배양후 Nitric TNF-$\alpha$ 및 IFN-$\gamma$를 ELISA로 정량하여 다음과 같은 결과를 얻었다. Nitrite 생성정도는 Fasciola 조항원으로 24시간 감작시킨 대식세포에서 가장 높게 나타났으며 (140$\mu$M/ml) Paragonimus 항원군에서는 24시간에 최고치에 달하였다가(34 $\mu$M/ml) 시간이 경과함에 따라 점차 감소하였다. IFN-$\gamma$는 Paragonimus 항원군에서만 대조군에 비해 높았으며 9일경에 최고치를 보였다(475ng/ml). TNF-$\alpha$는 Schistosoma 항원군에서는 nitric oxide의 생성과 분비 양상이 일치하였다. 위의 결과에 의하면, 흡충류항원으로 감작된 마우스 대식세포의 nitric oxide 생성에 영향을 미치는 cytokine의 종류는 흥충류에 따라 차이를 보였으며, 이 중 Paragonimus 항원에 의해서는 IFN-$\gamma$의 분비가 촉진되는 것으로 나타났고, Schistosoma 의 경우에는 TNF-$\alpha$가 nitric oxide의 생성에 관계함을 알 수 있었다.

• 대한약리학회지
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• 제32권3호
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• pp.389-397
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• 1996

위점막은 위강내에서 생성되는 독성이 강한 활성산소종에 노출된다. Nitric oxide는 glutathione의 항상성을 유지시킴으로써 acetaminophen 유도 간독성에 대한 보호효과를 나타내었다. 본 연구는 hydrogen peroxide로 인한 위선세포 손상에 대한 nitric oxide의 작용을 규명하고자 하였다. Hydrogen peroxide는 ${\beta}-D-glucose$와 glucose oxidase의 반응에 의해 생성시켰으며, 위선세포에 L-arginine, $N^{G}-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$을 전처리 한 후, 세포외로 유리되는 지질과산화물 및 nitrite를 정량하고 세포내 glutathione 함량을 측정하였다. 결과로서, glucose/glucose oxidase를 처리한 경우 glucose oxidase 농도의존적으로 지질과산화물 생성은 증가되었으며, nitrite 유리 및 glutathione 함량은 감소되었다. NO synthase의 기질인 L-arginine 전처리시 glucose/glucose oxidase에 의한 지질과산화 및 nitrite 유리 증가와 세포내 glutathione 감소등이 방지되었다. $N^G-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$등 NO synthase 억제제들은 세포손상에 보호효과를 나타내지 않았다. 결론적으로 nitric oxide는 hydrogen peroxide로 인한 세포손상에 대한 보호효과가 없으며, 이는 지질과산화 반응 및 세포내 glutathione 고갈등을 억제시킴으로써 이루어진다고 사료된다.

• Journal of Preventive Medicine and Public Health
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• 제30권2호
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• pp.369-380
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• 1997

Balb/c 마우스의 복강대식세포와 동종 마우스의 유선암에서 기원한 EMT-6 세포를 배양하는 조건에 여러 농도의 수은을 첨가하여 nitrite와 nitrite 생성의 변화를 관찰한 결과는 다음과 같다. 복강대식세포 및 EMT-6 세포가 생성하는 nitrite와 nitrate 양은 공히 배양시작 12시간 후에 생성량에 비해 24 시간 후에는 2배, 36시간 후에는 3배의 농도로 측정되었다. 이때 nitrite와 nitrate 농도 사이에 매우 밀접한 상관관계가 관찰되었다. 수음첨가에 따라 nitrite 및 nitrate 생성량은 용량 의존적 관계로 현저한 감소를 보이며, 24 시간 또는 36시간 후의 세포생존률도 역시 수은농도에 비례하여 감소되는데, 복강대식세포의 생존률 감소가 EMT-6 세포의 것에 비해 더욱 현저하였다. 이들 세포내에서 생성되는 ATP의 양은 복강세포의 경우 그 생존률과 비례하는 경향이었으나, EMT-6세포의 경우는 비교적 높은 생존률에도 불구하교 배양액내에 수은농도를 증가시킴에 따라 ATP생산은 현저히 감소하였다. 이상의 결과는 면역세포인 복강대식세포 뿐아니라 암세포인 EMT-6 세포에서도, L-arginine으로부터 nitric oxide를 생성하는 생화학적 반응이 수은에 의해 공히 억제될 수 있음을 보여준다. 한편 수은의 세포성 면역에 미치는 독성은 수은이 면역세포의 ATP생성과 관련한 에너지 대사과정의 장애을 초래하여 nitric oxide 생성에 필요한 반응에너지의 공급을 억제시키기 때문에 나타나는 현상으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.455-460
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• 1998

The present study was aimed at investigating whether the development of hypertension is related with an altered expression of nitric oxide synthases (NOS) in the kidney. By Western blot analysis, the expression of bNOS and ecNOS isoforms was determined in the kidney of deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2K1C) rats. In DOCA-salt hypertension, the expression of both bNOS and ecNOS was decreased, along with tissue contents of nitrites. In 2K1C hypertension, the nitrite content of the clipped kidney was decreased along with ecNOS levels, whereas neither the nitrite content nor the expression of NOS isoforms was significantly altered in the contralateral non-clipped kidney. These results suggest that the development of hypertension is associated with an altered renal expression of NOS and nitric oxide generation in DOCA-salt and 2K1C rats.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.55-59
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• 1999

Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation in rheumatic and autoimmune diseases. The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS by bacterial lipopolysaccaride (LPS) were examined in murine peritoneal macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by higenamine which at 0.01 mM, decreased nitrite/nitrate levels by $48.7{\pm}4.4%$This was comparable to the inhibition of LPS-induced nitrite/nitrate production by tetrandrin ($49.51{\pm}2.02%$). at the same concentration. Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 $\mu\textrm{g}$/m;; 18hrs) and higenamine (0.001, 0.,01 mM; 18hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages. The clinical implications of these findings remain to be established.