• Archives of Pharmacal Research
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• 제25권3호
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• pp.343-348
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• 2002

Carbon monoxide (CO) are produced by heme oxygenase (HO), and HO was detected in hypothalamus. However, the roles of CO produced in hypothalamus was not fully elucidated. So, we tested the effects of CO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. CO-saturated aCSF ($4{\;}{\mu}l$, i.c.v.) and hemin ($10{\;}{\mu}g$, i.c.v.) elicited marked febrile response. Pretreatment with indomethacin completely inhibited CO- and hemin-induced fever. Zinc protoporphyrin-IX ($10{\;}{\mu}g$, i.c.v.) or ODQ ($50{\;}{\mu}g$, i.c.v.) partially reduced hemin-induced febrile response. Dibutyryl-cGMP ($100{\;}{\mu}g$, i.c.v.) produced profound febrile response and this febrile response was attenuated by indomethacin. These results indicate that endogenous CO may have a role as a pyrogenic mediator in CNS and CO-mediated pyresis is dependent on prostaglandin production and partially on activation of soluble guanylate cyclase.

• 한국가금학회지
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• 제27권2호
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• pp.115-132
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• 2000

본 장에서는 양질의 계란생산에 필요한 난각과 난각색의 형성에 관해서 언급하였다. 강한 난각의 형성은 난각을 이루는 내적인 요인들 (큐티클층, 진각, 난각층의 조직)과 소화기, 난각형성에 관여하는 각종 체내 분비선, 신장, 호르몬 등의 적정기능에 의하여 결정된다. 병아리가 성성숙에 달하면 골수골은 산란계가 난각의 형성이 정점에 달했을 때를 대비 할 수 있는 정도가 되어야 한다. 난각이 형성되는데 중요한 기능을 갖는 요인들로는 산란계 사료중의 칼슘원, 산란계사료 중의 칼슘과 인의 비율, 비타민 D의 적정수준, 체액중의 각종 무기물 균형, 기타 영양소 수준들을 들 수 있다. 또 생리적, 환경적인 요인들과 산란계의 나이나 산란계사의 온도와 습도, 산란계의 계통, 질병, 계사에서 알의 수집부터 수송에 이르기까지의 각종 관리형태 등은 계한이 생산자에서부터 소비자에 이르기까지 여러 단계에서 나타나는 각종 난각 파괴의 요인이 된다. 난각에 나타나는 색소에 관여되는 요인들로는 protoporphyrin-IX, biliverdin-IX, 아연 등이 함유된 킬레이트와 때로 적은 양이 관여하기는 하지만 coproporphyrin-III 등이 포함된다. 그러나 이러한 요인들이 난각색의 형성에 관여하는 데에는 산란계의 연령, 질병, 약품 첨가 여부, 난각 형성도 중 난각 표면의 손상 여부 등 여러 가지가 관여된다.

• 동의생리병리학회지
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• 제18권4호
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• pp.1071-1077
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• 2004

Mudanpi (Cortex Moutan Radicis; the root cortex of Paeonia suffruticosa Andrews) is an important Chinese crude drug used in many oriental prescriptions. 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose (PGG), a major component of this crude drug, has been shown to possess potent antioxidant, anti-mutagenic and anti-proliferative effects. In this study, I examined whether PGG could protect Neuro 2A cells, a kind of neuronal cell lines, from oxidative damage through the induction of HO-1 expression and HO activity. Exposure of Neuro 2A cells to PGG (10-50μM) resulted in a concentration- and time-dependent induction of HO-1 mRNA, and protein expressions and heme oxygenase activity. PGG protected the cells from hydrogen peroxide-induced cell death. The protective effect of PGG on hydrogen peroxide-induced cell death was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. These results indicate that PGG is a potent inducer of HO-1 and HO-1 induction is responsible for the PGG-mediated cytoprotection against oxidative damage.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.268-282
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• 2016

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

• Journal of Ginseng Research
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• 제35권3호
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• pp.352-359
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• 2011

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on $H_2O_2$-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.

• Journal of Preventive Medicine and Public Health
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• 제28권2호
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• pp.421-432
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• 1995

The influence of lead exposure on renal function was studied. Eighty nine lead exposed workers who worked in 2 storage battery factories, and seventy one control workers were chosen for this study. Blood lead(PbB) and zinc protoporphyrin in whole blood(ZPP) were selected as indicators of lead exposure. As indicators of renal function, urinary N-acetyl-$\beta$-D-glucosaminidase(NAG), blood urea nitrogen(BUN), serum creatinine(S-Cr), total protein in urine(U-TP),and serum uric acid(S-Ua) were selected. The results obtained were as follows: 1. While the mean values of lead exposure indicators of lead workers were significantly different from non-exposed ones, the mean values of NAG, U-TP, BUN and S-Cr of renal function indicators of exposed were also significantly different from non-exposed but their mean values were all within normal limits. 2. BUN, logarithmic U-TP, logarithmic NAG and S-Cr showed statistically significant correlation with PbB. 3. The proportion of workers whose values of renal function indicators were over the normal limits(NAG7.5 U/g Cr ; U-TP10.9 mg/dl ; BUN20 mg/dl ; S-Crl.2 mg/dl ; S-Ua7.0 mg/dl) by the level of lead absorption in terms of PbB and ZPP were calculated. The proportion of workers with over the normal limits of U-TP among total workers showed the dose-response relationship. When age is adjusted, U-TP showed significantly strong dose-response relationship with the level of PbB and ZPP.

• 한국산업보건학회지
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• 제10권2호
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• pp.165-172
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• 2000

This study was carried out to investigate relationship between plasma $\delta$ - aminolevulinic acid (ALAP) and lead exposure indices in exposure to lead. The subjects were 218 male workers in 2 storage battery companies and 2 secondary smelting companies. Blood lead(PbB), blood zinc-protoporphyrin( ZPP), urinary $\delta$ - aminolevulinic acid (ALAU), hemoglobin(Hb), and hematocrit(Hct) were measured as lead exposure indices. The results were as follows, 1. The means of blood lead and blood ZPP concentration of subjects were $27.2{\pm}14.0{\mu}g/d{\ell}$ and $55.1{\pm}47.6{\mu}g/d{\ell}$, respectively. The means of plasma $\delta$ - ALA and urinary $\delta$ - ALA concentration were $18.9{\pm}25.1{\mu}g/d{\ell}$ and $2.1{\pm}4.6mg/{\ell}$, respectively. 2. The concentration of ALAP was $11.2{\mu}g/{\ell}$ for below $20{\mu}g/d{\ell}$ PbB, $12.8{\mu}g/{\ell}$ for from $21-40{\mu}g/d{\ell}$ PbB, and $51.2{\mu}g/{\ell}$ for over $40{\mu}g/d{\ell}$ PbB, respectively. 3. ALAP was significantly correlated with ALAU(r=0.829, p<0.01), ZPP(r=0.724, p<0.01) and PbB(r=0.552, p<0.01).

• Nutrition Research and Practice
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• 제8권4호
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• pp.352-359
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• 2014

BACKGROUND/OBJECTIVES: In this study, we determined the anti-inflammatory activities and the underlying molecular mechanisms of the methanol extract from Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells. MATERIALS/METHODS: The potential anti-inflammatory properties of ECM were investigated by using RAW264.7 macrophages. We used western blot assays and real time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. RESULTS: ECM significantly inhibited inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2) derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory effects of ECM were accompanied by decreases in LPS-induced nuclear translocations and transactivities of $NF{\kappa}B$. Moreover, phosphorylation of mitogen-activated protein kinase (MAPKs) including extracellular signal-related kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein expression at the protein levels in dose-dependent manner. However, zinc protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced suppression of NO production. CONCLUSIONS: These results suggested that ECM-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects. These findings suggest that ECM exerts anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of Erigeron Canadensis L.

• The Korean Journal of Physiology and Pharmacology
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• 제15권2호
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• pp.83-88
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• 2011

A large body of evidence has indicated that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In our previous study, cilostazol was found to increase the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) in synovial cells. Thus, the present study was undertaken to examine whether cilostazol is able to counteract tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced cell death in endothelial cells via the induction of HO-1 expression. We exposed human umbilical vein endothelial cells (HUVECs) to TNF-${\alpha}$ (50 ng/ml), with or without cilostazol ($10{\mu}M$). Pretreatment with cilostazol markedly reduced TNF-${\alpha}$-induced viability loss in the HUVECs, which was reversed by zinc protoporphyrine IX (ZnPP), an inhibitor of HO-1. Moreover, cilostazol increased HO-1 protein and mRNA expression. Cilostazol-induced HO-1 induction was markedly attenuated not only by ZnPP but also by copper-protoporphyrin IX (CuPP). In an assay measuring peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) transcription activity, cilostazol directly increased PPAR-${\gamma}$ transcriptional activity which was completely abolished by HO-1 inhibitor. Furthermore, increased PPAR-${\gamma}$ activity by cilostazol and rosiglitazone was completely abolished in cells transfected with HO-1 siRNA. Taken together, these results indicate that cilostazol up-regulates HO-1 and protects cells against TNF-${\alpha}$-induced endothelial cytotoxicity via a PPAR-${\gamma}$-dependent pathway.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.92-100
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• 2019

Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, prostaglandin (PG) $E_2$, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated $Akt/IKK/NF-{\kappa}B$ pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and $TNF-{\alpha}$ by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting $Akt/IKK/I{\kappa}B/NF-{\kappa}B$ pathway and promoting Nrf-2/HO-1 pathway.