• 대한수의학회지
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• 제55권3호
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• pp.199-204
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• 2015

4,4'-diaminodiphenyl sulfone (dapsone) is a sulfone drug that has antibacterial effects on a variety of bacteria, especially Mycobacterium leprae; thus, it has been used to treat leprosy. Previous studies demonstrated that dapsone inhibits integrin-mediated adherence of neutrophils and production of prostaglandin $E_2$ by polymorphonuclear leukocytes. Hence, dapsone may act in immune cells and regulate cell-mediated inflammation processes. However, its anti-inflammatory effects remain unclear. The present study demonstrated that dapsone modulates the production of inflammation-related cytokines in immune cells. We employed the spleen cells of mice, which are major immune cells, and lipopolysaccharide (LPS) as a causative agent of inflammation for experiments. Dapsone induced a proportional change in splenocyte subsets and the apoptosis of spleen cells. Interestingly, dapsone decreased the production of tumor necrosis factor-alpha and interleukin (IL)-10, but not IL-6, in LPS-treated spleen cells. In other assays, we measured the dapsone-induced production of nitric oxide (NO) and the expression of activation markers of spleen cells. Dapsone decreased NO production in LPS-treated spleen cells. Taken together, our results demonstrate that dapsone has anti-inflammatory effects in immune cells and provide new insight into the potential uses of this agent.

• 대한의생명과학회지
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• 제9권1호
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• pp.37-42
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• 2003

The present study was conducted to determine whether administration of heat extract of Lepidii Semen has an inhibitory effect on neutrophil-derived oxidative injury following dermal scald burn in rats. Acute lung injury was induced by scald burn (15% of TBSA) in rats. To identify acute edematous lung injury, protein concentrations and numbers of polymorphonuclear leukocytes were measured in bronchoalveolar lavage (BAL) at 5 h after skin burn. In addition, the level of lung KC (neutrophil chemoattractant cytokine) and activity of lung myeloperoxidase (MPO) were measured, and histopathological changes were observed as well. Lung weight and concentration of BAL protein, the index of lung injury, were clearly increased at 5 h postburn compared with those of sham-operated group. Administration of heat extract of Lepidii Semen after scald burn inhibited the production of KC in lung tissue and decreased the activity of lung MPO related to infiltration of neutrophils. In histopathological changes in lung tissue, infiltration of inflammatory cells and pulmonary edema induced by skin burn were decreased by administration of heat extract of Lepidii Semen after scald burn. These results suggest that Lepidii Semen may be an effective medical stuff for acute lung injury induced by skin burn.

• 한국임상수의학회지
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• 제23권4권
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• pp.393-399
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• 2006

전신마취제인 케타민은 흥분성 아미노산의 활성을 방해하는 N-methyl-D-aspartate (NMDA) 수용체의 비경쟁적인 길항제이다. 본 연구는 개 말초혈액 백혈구의 순간산소과소비현상(Oxidative burst activity; OBA)에 있어서 케타민의 효과를 검토하였다. 탐식세포의 OBA는 유세포 분석기로 분석하였다. 케타민을 말초혈액 다형핵백혈구(peripheral blood polymorphonuclear cells; PMN)와 monocyte-rich cells에 직접처리 하였을 때는 OBA가 감소하였으며, 또한 케타민을 처리한 말초혈액 단핵구세포(peripheral blood mononuclear cells; PBMC) 배양상층액에 의해서도 PMN과 monocyte-rich cells의 OBA가 감소하였다. 그러나 케타민을 처리한 PMN 배양상층액에 의해서는 탐식세포의 OBA에 있어서 아무런 변화가 없었다. 하지만 이러한 OBA의 감소는 latex beads를 넣어 탐식반응이 일어날 때만 측정되었다. 이상의 결과로부터 탐식반응이 일어나는 동안 케타민은 호중구와 단핵구와 같은 개 말초혈액 탐식구의 OBA에 있어 억제효과를 나타내었다.

• 대한예방한의학회지
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• 제4권2호
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• pp.170-192
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• 2000

Objectives : This study was carried out to research antioxidant effects of Sagunja-Tang(SA) through in vitro and vivo experiments, and tried to investigate the relation between oxidation of tissues and deficiency of Qi. Methods and results : HPLC analysis of glycyrrhizine - known to be the main compound of Radix Glycyrrhizae - was done to certify the quality of SA. Chemiluminescence was initiated by adding tort-butyl hydroperoxide (t-BHP) to rabbit polymorphonuclear leukocytes (neutrophils), and generated reactive oxygen species (superoxide anion) decreased significantly by SA as dose dependent manner. Cell injury during 60 minutes tissue incubation was initiated by adding t-BHP, a hydrophobic hydroperoxide and $H_2O_2$, an water soluble oxidant to rat renal cortical and liver slices. Percentage cell death and lipid peroxidation were estimated by measuring lactate dehydrogenase (LDH) and malondialdehyde (MDA), a product of lipid peroxidation. t-BHP induced % cell death of renal cortical slices and lipid peroxidation of renal cortical and liver slices were decreased significantly by SA. SA decreased significantly % cell death and lipid peroxidation of renal cortical and liver slices induced by $H_2O_2$, too. Acute renal and liver injury induced by $HgCl_2\;and\;CCl_4$, which initiated from free radical, were applied to mice and metabolic data were obtained. Data showed protective effects of SA on acute renal injury caused by decrease of glomerular filtration. SA protected acute liver injury too. Conclusions Through this study, we found that SA have antioxidant effects and tissue oxidation was similar to deficiency of Qi. And further studies have to be followed to certify the mechanisms.

• Clinical and Experimental Pediatrics
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• 제59권12호
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• pp.477-482
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• 2016

Purpose: We conducted a study to determine which factors may be useful as predictive markers in identifying Kawasaki disease (KD) patients with a high risk of resistance to intravenous immunoglobulin (IVIG) and developing coronary artery lesions (CAL). Methods: We enrolled 287 patients in acute phase of KD at a single center. The demographic, clinical and laboratory data were collected retrospectively. Results: There were 34 patients in the IVIG resistant group. The IVIG resistant group had significantly higher serum N-terminal-pro-brain natriuretic protein (NT-proBNP) levels (P<0.01) and polymorphonuclear neutrophil (PMN) percentage (P<0.01) in comparison to the IVIG responders. The results yielded sensitivity (78.8%, 60.6%), specificity (58.2%, 90%) and cutoff value (628.6 pg/mL, 80.3%) of NT-proBNP and PMN respectively, in predicting IVIG resistance. Despite IVIG administration, 13 of the 287 patients developed CAL. The patients in the CAL group had higher NT-proBNP levels (P<0.01) and higher PMN percentage (P<0.01). In these patients, the results yielded sensitivity (73.3%, 56.7%), specificity (67.9%, 88.9%) and cutoff value (853.4 pg/mL, 80.3%) of NT-proBNP and PMN respectively, for predicting CAL. The area under the curve (AUC) for predicting resistance to IVIG was NT-proBNP 0.712, PMN 0.802. The AUC for predicting CAL was NT-proBNP 0.739, and PMN 0.773. Conclusion: Serum NT-proBNP levels and PMN percentage were significantly elevated in patients with KD with IVIG resistance and CAL. Thus, they may be useful predicting markers for IVIG resistance and development of CAL in KD patients.

• 동의생리병리학회지
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• 제25권1호
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• pp.55-64
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• 2011

The object of this study was to observe the effects of Scutellariae Radix (SR) aqueous extracts on lipopolysaccharide (LPS)-induced rat acute lung injury. Five different dosages of SR extracts were orally administered once a day for 28 days before LPS treatments, and then 5 hours after lipopolysaccharide treatment, all rats were sacrificed. 8 groups, each of 16 rats per group were used in the present study. Changes on the body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid (BALF) protein, lactate dehydrogenase (LDH) and proinflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-1${\beta}$ (IL-1${\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde (MDA), myeloperoxidase (MPO), proinflammatory cytokine TNF-${\alpha}$ and IL-1${\beta}$ contents were observed with histopathology of the lung, changes on luminal surface of alveolus (LSA), thickness of alveolar septum, number of polymorphonuclear neutrophils (PMNs). The results were compared with a potent antioxidant ${\alpha}$-lipoic acid, 60 mg/kg, in which the effects on LPS-induced acute lung injury were already confirmed. The results obtained in this study suggest that over 125 mg/kg of SR extracts showed favorable effects on the LPS-induced acute lung injury, and 250 mg/kg of SR extracts resembling acute respiratory distress syndrome mediated by their antioxidant and anti-inflammatory effects and .as similar to ${\alpha}$-lipoic acid in the present study. Therefore, it is expected that SR will be showed favorable effects on the acute respiratory distress syndrome.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.183-189
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• 1999

This investigation is to determine whether the surface complexation of iron influence acute pulmonary responses induced by silica. For this study, three varieties of cation complexed silica were used: $silica-H^+,\;-Zn^{2+},\;and\;-Fe^{3+},$ since the first two are not active in the transport of electrons and generate little free radicals relative to the dust with the surface iron. Rats (270 to 280 g) were intratracheally (IT) instilled with saline, $silica-H^+,\;-Zn^{2+},\;or\;-Fe^{3+}$(5 mg in 0.5 ml saline). After 4 h, cell number, type, and differentiation were analysed in the bronchoalveolar lavage cells, and the levels of lactate dehydrogenase (LDH) and total protein were determined in the lavage fluid. In addition, bronchoalveolar lavage cells were cultured, and nitric oxide production was measured using nitrate assay. Inducible nitric oxide synthase (iNOS) mRNA in the bronchoalveolar lavage cells was also determined by northern blot analysis. Differential counts of the lavage cells showed that red blood cells were increased by 9-, 8-, and 13-fold and total leukocytes (lymphocytes plus polymorphonuclear neutrophils) by 48-, 36-, and 33-fold, following IT $silica-H^+,\;-Zn^{2+},\;and\;-Fe^{3+},$ respectively compared with the saline group. Meanwhile, there were no significant differences in red blood cells and total leukocytes among any of the cation complexed silica groups. The levels of LDH and total protein in the lavage fluid were significantly increased by 3- to 4-fold. However, compared among these silica groups, $Fe^{3+}$? complexation did not significantly change the LDH activity and total protein. NO production in cultured bronchoalveolar lavage cells was elevated by 2-fold, following IT any of the silica treatments compared with the saline group. Furthermore, the steady-state levels of iNOS mRNA in the lavage cells were greatly increased. There were any differences in iNOS mRNA expression among the silica-treated groups as with NO production. These findings suggest that surface complexed iron may not influence the acute pulmonary responses resulted from 4h exposure to silica.

• Korean Journal of Acupuncture
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• 제27권1호
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• pp.31-47
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• 2010

Objectives: To investigate the anti-inflammatory effects of cultivated wild ginseng pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods: Sprague-Dawley rats were divided into 4 groups; LPS control (n=6), LPS+cultivated wild ginseng pharmacopuncture at CV4 (n=6), LPS+cultivated wild ginseng pharmacopuncture at CV17 (n=6), and LPS+cultivated wild ginseng pharmacopuncture at Ex-HN1 (n=6). Pharmacopuncture (0.1 ml) was given every two days for 4 weeks followed by inflammation induction by peritoneal LPS injection (5 mg/kg). Blood, liver tissue, and peritoneal lavage fluid were taken and proinflammatory cytokines and other related factors were analysed. Results: Compared with the control group, CV4 and Ex-HN1 pharmacopuncture groups significantly attenuated plasma IL-$1{\beta}$, IL-6, and TNF-$\alpha$ increase at 2h and 5h after LPS injection (P<0.05). A significant difference from control group emerged at 5 h for plasma IL10 (P<0.05). For liver cytokines analyzed at 5 h after LPS injection, only CV4 pharmacopuncture group showed significant difference in TNF-$\alpha$ and IL-10 (P<0.05). Blood CD4/CD8 ratio and the phagocytic activities of polymorphonuclear neutrophils were not different from those of control group in all pharmacopuncture groups (P>0.05). CV4 pharmacopuncture significantly attenuated increase of plasma ${NO_3}^-/{NO_2}^-$, Intracellular adhesion molecule-1 (ICAM-1), cytokine-induced neutrophil chemoattractant-1 (CINC-1), and prostaglandin $E_2$ ($PGE_2$) compared with the control group (P<0.05). Monocyte chemoattractant protein-1, $PGE_2$, and CINC-1 level of CV4 pharmacopuncture group was significantly different from those from the control group (P<0.05). Conclusions: These results indicate that cultivated wild ginseng pharmacopuncture at CV4 may have a potent anti-inflammatory effect in an LPS-induced inflammatory rat model.

• 대한상한금궤의학회지
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• 제13권1호
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• pp.21-44
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• 2021

Objective : This study aimed to assess the preventive effect of Bupleuri Radix aqueous extracts (BR) and red koji-fermented BR (fBR) in lipopolysaccharide (LPS)-induced acute lung injury in a rat model. Methods : Rats were administered 30, 60, or 120 mg/kg/day of fBR for 28 days before LPS treatments. All rats were sacrificed 5 h after LPS treatment (500 ㎍/head, intratracheal instillation). Body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters (pH, partial pressure [Pa] of O2, PaCO2), bronchoalveolar lavage fluid (BALF) protein, lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total cell numbers, neutrophil/alveolar macrophage ratios, lung malondialdehyde (MDA), and myeloperoxidase (MPO) were measured. In addition, histopathological changes including the luminal surface of alveoli (LSA), thickness of alveolar septum, and number of polymorphonuclear neutrophils (PMNs) were checked. Results : LPS injection led to increases in lung weights, pulmonary transcapillary albumin transit, BALF protein, LDH, TNF-α and IL-1β contents, total cells, neutrophil and alveolar macrophage ratios, lung MDA, MPO, alveolar septum thickness, and PMNs, and decreases in PaCO2 and pH of arterial blood and LSA. However, these LPS-induced acute lung injuries were inhibited by pretreatment of 30, 60, and 120 mg/kg of fBR. The most favorable effects were seen with 30 mg/kg fBR as compared with 60 mg/kg of α-lipoic acid and BR. Conclusions : fBR showed preventive effects on LPS-induced acute lung injury, which resembles acute respiratory distress syndrome. The mechanisms of action were likely via antioxidant and anti-inflammatory means.

• 한국임상수의학회지
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• 제40권3호
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• pp.175-181
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• 2023

Fucoidan extracted from brown seaweed has a variety of biological activities. Neutrophil extracellular traps (NETs) formation is an immune response for the invasion of pathogens. Neutrophils release granule protein and chromatin that form extracellular fibers that bind microbes. These NETs degrade virulence factors and kill bacteria. The aim of this study was to investigate the effect of fucoidan on NET formation of porcine peripheral blood polymorphonuclear cells (PMNs). The NET formation was determined by fluorescence emission of propidium iodide (PI) in PMNs by a fluorescence microplate reader. The production of tumor necrosis factor (TNF)-α from peripheral blood mononuclear cells (PBMCs) was measured by ELISA method. Fucoidan itself did not show any direct effect on NET formation. However, NET formation of PMNs was increased by the culture supernatant from PBMCs treated with fucoidan. The NET formation of PMNs were also enhanced by treatment with recombinant porcine (rp) TNF-α. The ability of culture supernatant from PBMCs treated with fucoidan to increase the NET formation of PMNs was inhibited by addition of goat anti-rp TNF-α polyclonal antibody (pAb) (IgG) prior to the culture. The increase of NET formation by rp TNF-α was also inhibited by goat anti-rp TNF-α pAb (IgG). The level of TNF-α in culture supernatant from PBMCs was increased by treatment with fucoidan. These results suggest that fucoidan increases porcine NET formation, which is mediated by TNF-α produced from PBMCs.