• BMB Reports
• /
• 제30권2호
• /
• pp.89-94
• /
• 1997

In this study, during the activation of neutrophil responses by sodium fluoride. involvement of protein tyrosine kinase was studied. Respiratory burst lysosomal enzyme release and elevation of $[Ca^{2+}]_i$stimulated by sodium fluoride in neutrophils were inhibited by protein kinase inhibitors, genistein and tyrphostin. The inhibitory effect of genistein and tyrphostin on superoxide and $H_{2}O_{2}$ production was less than that of protein kinase C inhibitors, staurosporine and H-7. Staurosporine and H-7 had little or no effect on the release of myeloperoxidase and acid phosphatase stimulated by sodium fluoride. EGTA and verapamil inhibited the elevation of $[Ca^{2+}]_i$ evoked by sodium fluoride. The inhibitory effect of staurosporine on the elevation of $[Ca^{2+}]_i$ was less than that of genistein. Phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide production, which is sensitive to staurosporine, was further enhanced by genistein, whereas the stimulatory action of PMA on myeloperoxidase release was inhibited by genistein. A pretreatment of neutrophils with PMA signifcantly attenuated sodium fluoride-evoked elevation of $[Ca^{2+}]_i$ These results suggest that protein tyrosine kinase may be involved in the activation process of neutrophil responses due to direct stimulation of guanine nucleotide regulatory proteins. In neutrophil responses, PMA-stimulated neutrophils appear to show a different type of inhibition of protein tyrosine kinase.

• 대한약리학회지
• /
• 제20권1호
• /
• pp.1-11
• /
• 1984

인체 백혈구에서 추출한 myeloperoxidase(MPO)에 의한 NADH산화 및 methional에서의 ethylene 생성을 관찰하여 cell-free MPO/$H_2O_2/Cl^-$ system에서 관여하는 oxygen metabolites가 무엇인지를 규명하기 위하여 본 실험을 수행하였다. 1) NADH는 MPO/$H_2O_2/Cl^-$에 의하여 산화됨을 확인하였다. 즉 MPO, $H_2O_2$ 및 $Cl^-$가 존재하는 medium에서 NADH의 산화는 azide와 catalase에 의하여, 그리고 medium에서 $Cl^-$를 제거하였을 때 완전히 제거되었다. 2) 이와같은 MPO/$H_2O_2/Cl^-$에 의한 NADH산화는 $^1O_2$ 제거물질인 1,4-diazabicyclo(2,2,2) octane(DABCO)에 의하여 완전히 억제 되었으나 $OH{\cdot}$의 제거물질인 mannitol, benzoate, formate 및 methanol에 의해서는 영향을 받지 아니하였다. 3) 또한 methinal을 MPO/$H_2O_2/Cl^-$으로 처리하였을 때는 ethylene이 전혀 검출되지 아니하였으나 기타 $OH{\cdot}$을 생성할 것으로 알려진 산화계인 xanthine/xanthine oxidase 및 $Ca^{++}-H_2O_2$에 의해서는 현저한 ethylene생성을 관찰하였다. 이상의 결과는 Cell-free MPO/$H_2O_2/Cl^-$ 산화계에서는 $^1O_2$이 산화반응에 관여하는 주된 산소 대사물이며 $OH{\cdot}$은 생성되지 아니함을 알 수 있었다.

• Tuberculosis and Respiratory Diseases
• /
• 제60권1호
• /
• pp.83-91
• /
• 2006

연구배경 : 아스피린이 출혈성 쇼크시 나타나는 급성 폐손상에 미치는 효과와 혈장 및 폐세척액 내 ferritin 농도변화를 알아보고자 본 연구를 시행하였다. 방 법 : 실험동물은 체중 350g 내외의 Sprague-Dawley 종 흰쥐를 사용하였고, 혈압측정 및 출혈을 시키기 위하여 catheter를 양쪽 대퇴동맥에 삽입하였다. 수술 후 polygraph를 이용하여 평균동맥압을 기록하였으며, 출혈은 withdrawal pump를 이용하여 5분간 체중 kg당 20 ml의 혈액을 출혈시켰다. 실험군은 대조군, 출혈군과 아스피린 처치군으로 분류하였다. 대조군은 출혈군과 동일하게 수술하고 출혈은 시키지 않았으며 나머지 과정은 출혈군과 동일하게 처리하였다. 아스피린 처치군은 출혈 30분 전 대퇴정맥으로 아스피린(10mg/kg)을 주입하였고, 출혈군은 체중 당 동일한 양의 생리식염수를 주입하였다. 출혈 2시간 후의 폐손상 정도와 아스피린이 이에 미치는 효과를 알아보기 위하여 폐장내 myeloperoxidase 활성도와 폐세척액 내의 단백함량과 백혈구 수 및 혈장 ferritin 농도와 폐세척액 내 ferritin 농도를 측정하였다. 결 과 : 폐장내 myeloperoxidase 활성도와 폐세척액 내의 단백함량과 백혈구수는 출혈 후 대조군에 비해 유의하게 증가하였다. 이러한 반응은 아스피린 전처치에 의하여 효과적으로 차단되었다. 혈장 및 폐세척액 내 ferritin 농도는 출혈 후 크게 증가하였는데, 아스피린 전처치로 반응이 억제되었다. 결 론 : 심한 출혈 후에 생기는 급성 폐손상은 아스피린 전처치로 효과적으로 예방될 수 있으며, 출혈 후 증가하는 혈장 및 폐세척액 내 ferritin 농도는 급성폐손상이 나타날 수 있는 환자에서 조기진단을 위한 생체지표 로 활용될 수 있다고 생각된다.

• Tuberculosis and Respiratory Diseases
• /
• 제54권5호
• /
• pp.522-531
• /
• 2003

연구배경 : 급성 폐손상을 일으키는 요인중의 하나인 출혈성쇼크시 나타나는 급성 폐손상의 양상과 아스피린이 이에 미치는 효과를 알아보고자 본 연구를 시행하였다. 방법 : 실험동물은 체중 350g 내외의 Sprague-Dawley 종흰쥐를 사용하였고, 혈압측정 및 출혈을 시키기 위하여 catheter를 양쪽 대퇴동맥에 삽입하였다. 수술 후 polygraph를 이용하여 평균동맥압을 기록하였으며, 출혈은 withdrawal pump를 이용하여 5분간 체중 kg 당 20 ml의 혈액을 출혈시켰다. 실험군은 대조군, 출혈군과 아스피린 처치군으로 분류하였다. 대조군은 출혈군과 동일하게 수술하고 출혈은 시키지 않았으며 나머지 과정은 출혈군과 동일하게 처리하였다. 아스피린 처치군은 출혈 30분전 대퇴정맥으로 아스피린 (10mg/kg)을 주입하였고, 출혈군은 체중 당 동일한 양의 생리식염수를 주입하였다. 이상의 처치 후 2시간 또는 24시간 동안 cage에서 자유롭게 활동하도록 하였으며, 출혈후의 폐손상 정도와 아스피린이 이에 미치는 효과를 알아보기 위하여 폐장내 myeloperoxidase 활성도와 폐세척액 내의 단백함량과 백혈구 수를 측정하였다. 결과 : 폐장내 myeloperoxidase 활성도와 폐세척액 내의 단백함량과 백혈구수는 출혈 2시간 및 24시간 후 대조군에 비해 유의하게 증가하였다. 이러한 반응은 아스피린 전처치에 의하여 효과적으로 차단되었다. 결론 : 이상의 결과로 심한 출혈 후에 급성 폐손상이 생길 수 있으며 이는 아스피린 전처치로 효과적으로 예방될 수 있다고 생각된다.

• Journal of Ginseng Research
• /
• 제44권3호
• /
• pp.483-489
• /
• 2020

Background: Korean Red Ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for curing cardiovascular problems. The present study show the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, and biochemical parameters and histopathological findings. Methods: Animals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n = 9, each group). The animals were administered with KRG (250 and 500 mg/kg) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24-h interval) on the 8th and 9th day. Electrocardiography and echocardiography were performed to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. In addition, the dose of troponin I and activity of myeloperoxidase in serum and cardiac tissue were analyzed, and the histopathological findings were evaluated using light microscopy. Results: Administration of KRG at a dose of 250 and 500 mg/kg recovered electrocardiographic changes, ejection fraction, fractional shortening, left ventricular systolic pressure, the maximal rate of change in left ventricle contraction (-dP/dt_max), and left ventricle relaxation (-dP/dt_max). In addition, KRG treatment significantly normalized the oxidative stress markers in plasma, dose dependently. In addition, the values of troponin I and myeloperoxidase were ameliorated by KRG treatment, dose dependently. And, KRG treatment showed better histopathological findings when compared with the DOX control group. Conclusion: These mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological abnormality, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study show protective effects of KRG on cardiac toxicity.

• 대한한방내과학회지
• /
• 제31권4호
• /
• pp.731-751
• /
• 2010

Objectives : The present study aimed to find out the effect of Sagunja-tang on the prevention and treatment of inflammatory bowel disease using mice with TNBS-induced inflammatory bowel disease. Methods : Mice with TNBS-induced inflammatory bowel disease were medicated with Sagunja-tang, and the weight changes, colon length, lipid peroxidation, and myeloperoxidase activity were observed. Levels of the inflammatory markers interleukin (IL)-$1{\beta}$ and cyclooxygenase-2 (COX-2), its transcription factor activation, phospho-NF-${\kappa}$B (pp65), in the colon by enzyme-linked immunosorbent assay and immunoblot analysis were also measured. Finally, the activation of fecal bacterial enzyme, ${\beta}$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG) and hyaluronic acid were observed. Results : We found that oral administration of Sagunja-tang inhibited TNBS-induced colon shortening and also inhibited myeloperoxidase activity in the colon of mice as well as IL-$1{\beta}$ and COX-2 expression. Sagunja-tang also inhibited TNBSinduced lipid peroxidation and pp65 activation in the colon of mice. In addition, Sagunja-tang inhibited ${\beta}$-glucuronidase activation and fecal hyaluronic acid degradation activation. Conclusions : It is supposed that Sagunja-tang has a potential therapeutic effect on inflammatory bowel disease through the inhibition of both NF-${\kappa}$B activation and lipid peroxidation, and the improvement of intestinal conditions.

• Biomolecules & Therapeutics
• /
• 제21권5호
• /
• pp.398-404
• /
• 2013

During a screening program to search the anticolitic herbal medicines, 80% ethanol extract of the rhizome of Anemarrhena asphodeloides (AA) was found to potently inhibit the expression of proinflammatory cytokines TNF-${\alpha}$ and IL-1${\beta}$, as well as the activation of NF-${\kappa}B$ in LPS-stimulated colonic macrophages, followed by that of the rhizome of C. chinensis (CC). AA also potently inhibited TNBS-induced colitic markers, shortening of the colon and increase of macroscopic score, myeloperoxidase activity, TNF-${\alpha}$, IL-1${\beta}$, and IL-6, in mice. The synergistic effect of CC against the anticolitic effect of AA was investigated. CC synergistically inhibited the anticolitic effect of AA. AC-mix (AA+CC, 1:1) potently inhibited them. AC-mix also inhibited the activation of NF-${\kappa}B$, as well as the expression of TNF-${\alpha}$, IL-1${\beta}$, IL-6, iNOS and COX-2. The effects of AC-mix against oxazolone-induced colitis were investigated in mice. AC-mix also potently inhibited oxazolone-induced inflammatory markers, colon shortening, macroscopic score, myeloperoxidase activity, NF-${\kappa}B$ activation and proinflammatory cytokines. Overall, the anti-colitic effect of AC-mix was superior to that of mesalazine. Based on these findings, AC-mix may improve colitis by inhibiting NF-${\kappa}B$ activation.

• 대한한방내과학회지
• /
• 제26권2호
• /
• pp.379-389
• /
• 2005

Objectives: It is well known that aging and aging-related diseases are linked to the increased level of oxidative stress caused by reactive oxygen species(ROS) and reactive nitrogen species(RNS). Nonprotein-SH decreases during aging, while substances such as ROS, nitric oxide(NO), peroxynitrite($ONOO^-$), myeloperoxidase(MPO), and dityrosine show a significant increase. This study investigated the effect of Ichungwhan on the aging process by examining its effect on the generation of the above-mentioned substances. Methods: Four comparison groups of SD rats were used. They were 6 month-old rats, 24 month-old rats, and 24 month-old rats fed with food containing 0.1% and 0.3% of Ichungwhan extract. The amount of NO, $ONOO^-$, and ROS in the rats' kidneys were examined using a fluorescence microplate reader. The reagents used for this purpose include: dihydrorhodamine 123 (DHR 123), 2',7' -dichlorodihydrofluorescein, diacetate(DCFDA), and 4,5-diaminofluorescein(DAF-2). A spectrophotometer was used to investigate the reactivity of nonprotein-SH and myeioperoxidase(MPO), using reagents such as trichloroacetic acid(TCA) and tetramethylbenzidine(TMB). The amounts of MPO protein and dityrosine were measued by western blot. Results: The observed effects of Ichungwhan on rats were as follows: increase of nonprotein-SH; effective decrease of RNS level by suppression of the generation system of $ONOO^-$ and NO; decrease of ROS level; decrease of the MPO reactivity and the subsequent reduction of amount of MPO protein; retardation of dityrosine formation. It can be hypothesized, therefore, that Ichungwhan affects both the earlier and later phases of the molecular inflammatory process, and retards the aging process. Conclusions: Empirical evidence in this study supports a role for Ichungwhan in generation mechanisms of aging process-linked substances ROS, NO, $ONOO^-$, nonprotein-SH, MPO and dityrosine. Affects contrary to the aging process observed in rats beg further empiricism to investigate potential application of Ichungwhan as a medication for age-related diseases in humans.

• Archives of Plastic Surgery
• /
• 제33권5호
• /
• pp.621-626
• /
• 2006

Purpose: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied mainly in cardiovascular and neuronal systems. This study was planned to investigate the effects of recombinant human erythropoietin on ischemia-reperfusion injury in rat TRAM flap model. Methods: Superiorly based TRAM flap was elevated and ischemic insult was given for four hours. Thirty minutes before reperfusion, single dose recombinant human Erythropoietin(5000IU/kg) was injected via intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, malonyldialdehyde amount, nitric oxide content, tissue water content and histologic finding of inflammation was evaluated. On 10 days postoperatively, flap survival rate, angiogenesis and change in hematocrit level was evaluated. Results: Tissue nitric oxide level was significantly higher and myeloperoxidase activity was significantly lower in the treatment group 24 hours after reperfusion. Tissue water content was significantly lower in the treatment group. Perivascular neutrophil infiltration and intravascular adhesion was marked in the control group. Mean flap survival after ten days was 69% in the treatment group, and 47% in the control group, demonstrating a significant difference. Neovascularization in the treatment group also outnumbered the control group. No significant hematocrit rise was noted ten days after erythropoietin administration. Conclusion: Recombinant human Erythropoietin improved flap survival in ischemia-reperfusion injured rat TRAM flaps, at least partially owing to suppressed inflammation, increased nitric oxide, and enhanced angiogenesis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권1호
• /
• pp.109-117
• /
• 1998

Role of $Ca^{2+}$/calmodulin complex in intracellular $Ca^{2+}$ mobilization in neutrophils has not been clearly elucidated. In this study, effects of chlorpromazine, trifluoperazine and imipramine on the intracellular $Ca^{2+}$ mobilization, including $Ca^{2+}$ influx, in C5a-activated neutrophils were investigated. Complement C5a- stimulated superoxide production and myeloperoxidase release in neutrophils were inhibited by chlorpromazine, trifluoperazine and imipramine, except no effect of imipramine on myeloperoxidase release. A C5a-elicited elevation of [$Ca^{2+}$]i in neutrophils was inhibited by chlopromazine, trifluoperazine, imipramine, staurosporine, genistein, EGTA, and verapamil but not affected by pertussis toxin. The intracellular $Ca^{2+}$ release in C5a-activated neutrophils was not affected by chlorpromazine and imipramine. Chlorpromazine and imipramine inhibited $Mn^{2+}$ influx by C5a-activated neutrophils. Thapsigargin-evoked $Ca^{2+}$ entry was inhibited by chlorpromazine, trifluoperazine, imipramine, genistein, EGTA and verapamil, while the effect of staurosporine was not detected. The results suggest that $Ca^{2+}$/calmodulin complex is involved in the activation process of neutrophils. The depressive action of calmodulin inhibitors on the elevation of cytosolic $Ca^{2+}$ level in C5a-activated neutrophils appears to be accomplished by inhibition of $Ca^{2+}$ influx from the extracellular medium.