• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.405-414
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• 1999

The role of platelet-activating factor (PAF) was investigated in intestinal ischemia/reperfusion (I/R) induced acute lung injury associated with oxidative stress. To induce acute lung injury following intestinal I/R, superior mesenteric arteries were clamped with bulldog clamp for 60 min prior to the 120 min reperfusion in Sprague-Dawley rats. Acute lung injury by intestinal I/R was confirmed by the measurement of lung leak index and protein content in bronchoalveolar lavage (BAL) fluid. Lung leak and protein content in BAL fluid were increased after intestinal I/R, but decreased by WEB 2086, the PAF receptor antagonist. Furthermore, the pulmonary accumulation of neutrophils was evaluated by the measurement of lung myeloperoxidase (MPO) activity and the number of neutrophils in the BAL fluid. Lung MPO activity and the number of neutrophils were increased (p＜0.001) by intestinal I/R and decreased by WEB 2086 significantly. To confirm the oxidative stress induced by neutrophilic respiratory burst, gamma glutamyl transferase (GGT) activity was measured. Lung GGT activity was significantly elevated after intestinal I/R (p<0.001) but decreased to the control level by WEB 2086. On the basis of these experimental results, phospholipase $A_2\;(PLA_2),$ lysoPAF acetyltransferase activity and PAF contents were measured to verify whether PAF is the causative humoral factor to cause neutrophilic chemotaxis and oxidative stress in the lung following intestinal I/R. Intestinal I/R greatly elevated $PLA_2$ activity in the lung as well as intestine (p<0.001), whereas WEB 2086 decreased $PLA_2$ activity significantly (p<0.001) in both organs. LysoPAF acetyltransferase activity, the PAF remodelling enzyme, in the lung and intestine was increased significantly (p<0.05) also by intestinal I/R. Accordingly, the productions of PAF in the lung and intestine were increased (p<0.001) after intestinal I/R compared with sham rats. The level of PAF in plasma was also increased (p<0.05) following intestinal I/R. In cytochemical electron microscopy, the generation of hydrogen peroxide was increased after intestinal I/R in the lung and intestine, but decreased by treatment of WEB 2086 in the lung as well as intestine. Collectively, these experimental results indicate that PAF is the humoral mediator to cause acute inflammatory lung injury induced by intestinal I/R.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.85-85
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• 2001

Sam-Hwang-Sa-Shim-Tang(SHSST), a traditional Chinese medicine, composed of Rhei rhizoma, Scutellaria radix, and Coptidis rhizoma were used in the several disease including hypertension, constipation, and hemorrhage. In the present study, we investigated the neuroprotective effects of SHSST and its ingredients on the ischemia/ reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min and reperfusion was continued for 22 h. SHSST (450 mg/kg), Rhei rhii oma (100 mg/kg), Coptidis rhizoma (100 mg/kg), and Scutellaria radik (100 mg/kg) were orally administered twice, promptly prior to reperfusion and 2 h after the repefusion. Total infarction volume in the ipsilateral hemisphere of ischemia/ reperfusion rats was significantly lowed by the treatments of SHSST (39.2%) and Scutellaria radix (66.5%). However, Coptidis rhizoma did not show any significant effects on the total infarct volume. The inhibiting effect of Scutellaria radix on the total infarct volume was more potent than that of SHSST. In addition, Scutellaria radix significantly inhibited myeloperoxidase (MPO) activity, an index of neutrophil infiltration in ischemic brain tissue. However, there was marked mismatch between total infarct volume and MPO activity in the Scutellaria radix-treated rats. Our findings suggest that Scutellaria radix as an ingredient of SHSST plays a protective role in ischemia-induced brain injury by inhibiting neutrophil infiltration. The effects of Rhei rhizoma on transient brain ischemia-induced neuronal injury are under study.

• Journal of Korean Neurosurgical Society
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• 제59권4호
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• pp.334-340
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• 2016

Objective : The aim of our study was to evaluate the neuroprotective functions of the combination therapy using methylprednisolone (MP) and tranilast (TR) after spinal cord injury (SCI) in adult rats. Methods : Spinal cord compression injury model was achieved using Yasargil aneurysm clip. Rats were divided into control group, MP group, TR group, and combination therapy group using TR and MP. Rat models were assessed for locomotor functional recovery using Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content and myeloperoxidase (MPO) activity 24 hours post SCI, haematoxylin and eosin staining and glial fibrillary acid protein (GFAP) staining at 7 and 14 days post SCI. Results : The spinal cord water content and MPO activity in the combination therapy group was significantly lower than the control group and the individual therapy groups p<0.05. The combination therapy group had significantly higher BBB scores than control group and individual therapy groups (p<0.05). At one week after SCI, GFAP expression in the combination group was significantly lower than the control group (p<0.05) but there was no significant difference compared to the individual therapy groups (p>0.05). At 2 weeks after SCI there was a slight decrease in GFAP expression compared to the first week but the difference was not statistically significant (p>0.05), GFAP expression between the groups was not statistically significant p>0.05. Conclusion : Combining MP and TR is therapeutically more effective in improving functional recovery, inhibiting inflammation and glial scar formation after acute SCI.

• Archives of Pharmacal Research
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• 제21권5호
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• pp.531-536
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• 1998

We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trintrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg.day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. also, colon weight as an index of tissue edema, which was mardedly increased in the IBD rats, became significantly lower after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also colon weitht as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taruine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. the taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.

• 약학회지
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• 제42권2호
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• pp.205-213
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• 1998

The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30mg TNBS in 50% ethanol (0.5ml) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene $B_4$ ($LTB_4$) level were observed. The colitic rats received DA6034 (0.3-30mg/kg) or sulfasalazine (50-100mg/kg), prednisolone (0.3-3mg/kg) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic $LTB_4$ synthesis and MPO activity. This study show, therefore, that DA-6034 is effective m attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on $LTB_4$ synthesis and MPO inhibition.

• Tuberculosis and Respiratory Diseases
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• 제54권5호
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• pp.532-541
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• 2003

연구배경 : 장의 재관류로 발생하는 급성폐손상에서 group II $PLA_2$의 억제제로 알려진 doxycyclin의 치료효과와 그 작용기전을 알아보기 위하여 본 연구를 시행하였다. 특히 장의 재관류에 의한 급성폐손상이 호중구에 의한 산화성 스트레스에 의하며 이 과정에서 group II $PLA_2$가 관여한다는 사실에 근거하여 doxycyclin의 산화성 스트레스억제를 확인하는 것이 본 연구의 목적이었다. 방법 : 체중 300g 내외의 Sprague-Dawley 흰쥐에서 상장간막동맥을 60분간 clamp한 뒤 120분간의 재관류를 시키면 급성폐손상이 유도된다. 이때 호중구에 의한 산화성스트레스가 유발되고 여기에 $PLA_2$가 관여하는 것을 관찰하기위해 lung leak, lung MPO 활성도, CeCl3 cytochemical electron microscopy, cytochrome-c reduction assay 및 lung $PLA_2$ 활성도를 측정하였다. 또한 doxycyclin의 효과를 확인하기 위하여 doxycyclin hyclate(10mg/kg)를 복강내 주사한 뒤 위에서 언급한 모든 parameter를 측정, 비교하였다. 결과 : 장의 재관류로 유도된 급성폐손상에서 doxycyclin은 폐손상을 감소시켰는데 이것은 doxycyclin에 의한 lung MPO, 산소기생성, lung $PLA_2$ 활동도의 감소에 의한 것으로 생각되었다. 결론 : 장의 재관류로 유도된 급성폐손상은 호중구에서 생성되는 산소기, 특히 $PLA_2$의 활성화에 의해 생성된 산소기에 의한 것으로 생각되며 이때 doxycyclin은 $PLA_2$를 억제하여 산화성 스트레스를 감소시킴으로서 폐손상의 감소를 가져오는 것으로 생각된다.

• 한국약용작물학회지
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• 제13권6호
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• pp.245-249
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• 2005

신이는 전통적으로 비염 등의 치료에 사용되어 왔는데, 신이 에탄올 추출물은 그람 양성균인 Staphylococcus aureus 그람 음성균인 Pseudomonas fluorescens균 및 곰팡이균인 Aspergillus niger에 대하여 모두 항균활성을 보였으며, proteinase로 활성화된 receptor-2에 의한 흰쥐 뒷발바닥 부종모델에서 신이 에탄올 추출물을 경구투여한 경우 typsin이나 $tc-NH_2$로 유발된 발바닥 부종, 혈관투과성, myoloperoxidase 활성도에서 유의성 있는 억제율을 보여 항염증 활성이 뚜렷함을 나타냈다.

• Tuberculosis and Respiratory Diseases
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• 제62권4호
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• pp.299-307
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• 2007

배경: HMGB1은 염증반응의 후기에 분비되는 중요한 염증유발물질 중 하나이다. 본 연구에서는 기존에 염증유발물질로 잘 알려진 LPS와 새롭게 염증유발물질로 관심을 받고 있는 HMGB1의 염증유발작용을 생체 외 및 생체 내 실험을 통해 비교하고자 하였다. 또한 HMGB1의 자극에 의한 IL-8 promoter region의 활성화에 중요한 역할을 수행하는 전사인자들을 확인하고자 하였다. 방법: RAW264.7 세포에 LPS(100 ng/ml) 또는 HMGB1(500 ng/ml)을 투여하고 각각 0, 2, 4, 8, 12 그리고 24시간 뒤에 세포상층액의 $TNF-{\alpha}$, MIP-2 그리고 $IL-1{\beta}$의 농도를 ELISA법으로 측정하였다. 생쥐의 복강에 LPS(5 mg/kg) 또는 HMGB1(2.5 mg/kg)을 주입하여 급성폐손상을 유발한 후에 폐의 사이토카인의 발현과 MPO 활성도를 측정하였다(LPS는 4시간 뒤, HMGB1은 24 시간 뒤). IL-8 promoter 부위에 있는 NF-IL6, $NF-{\kappa}B$ 그리고 AP-1에 대한 결합부위에 대해 돌연변이를 일으킨 후에 각각의 돌연변이체를 pIL-6luc에 결합시킨 뒤 RAW264.7 세포에 삽입하였다. 이 세포들을 36시간 배양한 후에 HMGB1(500 ng/ml)으로 자극하고, 한 시간 뒤에 세포를 녹인 후 luciferase 활성도를 측정하였다. 결과: LPS 투여 후에 RAW264.7 세포 배양상층액의 $TNF-{\alpha}$농도는 24시간 뒤에, MIP-2 농도는 8시간 뒤에 최고치를 보였다. 한편 HMGB1 투여 후에는 $TNF-{\alpha}$와 MIP-2 농도 모두 24시간 뒤에 최고치를 나타내었다. LPS 복강 내 투여 후 4시간 뒤에 생쥐의 폐의 $TNF-{\alpha}$, MIP-2 그리고 $IL-1{\beta}$의 농도는 대조군에 비해 현저히 증가하였으나, HMGB1 복강 내 투여 후 24시간 뒤에 생쥐의 폐에서는 $IL-1{\beta}$의 농도만 약간 증가하였다. MPO 활성도는 LPS와 HMGB1 투여 후에 모두 증가하였으며, LPS 투여 후가 더 의미있게 증가하였다. $NF-{\kappa}B$ 돌연변이체와 AP-1 돌연변이체에서 luciferase 활성도가 의미있게 감소하였다. 결론: 이상의 결과를 살펴볼 때 HMGB1은 염증유발효과는 LPS에 비해 강도가 떨어지나 지속시간은 오래 계속되는 것으로 보이며, HMGB1에 의한 IL-8의 활성화에 $NF-{\kappa}B$ 뿐만 아니라 AP-1도 중요한 역할을 수행하는 것으로 판단된다.

• Korean Journal of Acupuncture
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• 제25권2호
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• pp.159-177
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• 2008

Objectives : Crohn's disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is need to develop new therapeutic methods or drugs that have few side effects in order to treat this disease. Acupuncture with Moxi-tar at Cheonchu (ST25) has anti-inflammatory properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects and speculated the mechanisms of acupuncture with Moxi-tar at ST25 on trinitrobenzene sulfonic acid (TNBS) induced colitis in mice which is a well known Crohn's disease animal model. Methods : 5 % TNBS was treated at day 1 and day 7 into rectum of mice. To investigate therapeutic effects of acupuncture with Moxi-tar at ST25, acupuncture was carried out on day 3, and day 6. For the data analysis, we observed macroscopic and microscopic findings of the colon. Weight and width of the colon, degree of damage, changes of body weight, and myeloperoxygenase (MPO) activity were checked. For analysing protein expression, we carried out immunohistochemical staining and Western blot. For analysing mRNA expression, RT-PCR was carried out. Results : TNBS induced damages on the colon of mice, while acupuncture of Moxi-tar at ST25 suppressed TNBS mediated damages similar to those on the colons of mice in the control (not treated with TNBS) group. The average body weight of TNBS treated mice (77.4%) was decreased compared with that of the control mice (105%), and acupuncture with Moxi-tar at ST25 suppressed the loss of body weight caused by TNBS (from 77.4% to 95.3%). TNBS induced infiltration of immune cells in all layers of the colon while acupuncture with Moxi-tar at ST25 suppressed infiltration of immune cells caused by TNBS. Furthermore, acupunctured with Moxi-tar at ST25 suppressed macro-, micro- colonic damages caused by TNBS. Acupunctured with Moxi-tar at ST25 dramatically improved the clinical and histopathological symptoms such as the increase in weight of the distal colon and the MPO activity in TNBS-induced colitis. Acupuncture with Moxi-tar at ST25 down-regulated the nuclear transcription factor kappa B ($NF-{\kappa}B$) activity and suppressed tumor necrosis factor-a (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-1${\beta}$), and intracellular adhesion molecule-1 (ICAM-1) expressions caused by TNBS. Conclusions : Acupuncture with Moxi-tar at ST25 helps recovery from the TNBS-induced colonic damage by down-regulation of $NF-{\kappa}B$ activity and suppressing of TNF-${\alpha}$, IL-1${\beta}$, and ICAM-1 expressions. This may be an important method for the treatment of Crohn's disease.

• Asian-Australasian Journal of Animal Sciences
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• 제24권2호
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• pp.250-257
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• 2011

An experiment was conducted to determine the effects of different mycotoxin adsorbents including esterified glucomannan (EGM), hydrated sodium calcium aluminosilicate (HSCAS) and compound mycotoxin adsorbent (CMA) on performance, blood parameters, and liver pathological changes in broilers fed mold-contaminated feed. Two hundred and forty 10-day-old broilers were randomly assigned to one of the five dietary treatments including: i) control diet; ii) mold-contaminated diet; iii) moldcontaminated diet+0.05% EGM; iv) mold-contaminated diet+0.2% HSCAS; v) mold-contaminated diet+0.1% CMA. At 35-days-old, blood and liver tissue samples were collected for analysis. 0.1% CMA improved ADG and ADFI during 10-42 d compared to the moldcontaminated group (p<0.05). The mold-contaminated diet increased total white blood cell (WBC) number, haemoglobin (Hgb) concentration, hematocrit (Hct) level, serum aspartate aminotransferase (AST) and ${\gamma}$-glutamyl transferase (GGT) activities, and decreased red blood cell (RBC) number and serum globulin (GLB) and urea nitrogen (BUN) concentrations (p<0.05). The three mycotoxin adsorbents alleviated the alteration of RBC, WBC, Hgb and AST caused by the mold-contaminated diet. Furthermore, 0.1% CMA increased GLB concentration and decreased Hct level and GGT activity (p<0.05). Liver superoxide dismutase (SOD) activity was reduced, and myeloperoxidase (MPO) activity was increased by the mold-contaminated diet (p<0.05). Both EGM and HSCAS prevented the increase of MPO activity (p<0.05). Liver lesion, including severe vacuolar degeneration of hepatocytes, was observed in chicks fed the mold-contaminated diet. 0.05% EGM prevented these effects except for biliary hyperplasia and mild vacuolar degeneration. 0.2% HSCAS showed medium vacuolar degeneration of hepatocytes. Liver of broilers fed 0.1% CMA revealed a mild vacuolar degeneration. These results indicate that a mold-contaminated diet results in adverse effects on blood parameters and liver morphology. 0.05% EGM and 0.2% HSCAS partially alleviated the adverse effects. However, 0.1% CMA almost completely ameliorated the adverse effects.