• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.219-226
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• 2000

In order to elucidate the role of platelet activating factor (PAF) in the acute lung injury induced by endotoxin (ETX), activities of phospholipase A2, lyso PAF acetyltransferase and oxidative stress by neutrophilic respiratory burst were probed in the present study. To induce acute lung injury, $100\;{\mu}g$ of E.coli ETX (type 0127; B8) was instilled directly into the tracheae of Sprague-Dawley rats. Five hours after the ETX instillation, induction of acute lung injury was confirmed by lung leak index and protein contents in the bronchoalveolar lavage (BAL) fluid. At the same time, lung phospholipase A2 (PLA2) activity and expression of group I and II secretory type PLA2 were examined. In these acutely injured rats, ketotifen fumarate, known as lyso PAF acetyltransferase inhibitor and mepacrine were administered to examine the role of PAF in the pathogenesis of the acute lung injury. To know the effect of the ETX in the synthesis of the PAF in the lungs, lyso PAF acetyltransferase activity and PAF content in the lungs were measured after treatments of ETX, ketotifen fumarate and mepacrine. In addition, the role of neutrophils causing the oxidative stress after ETX was examined by measuring lung myeloperoxidase (MPO) and enumerating neutrophils in the BAL fluid. To confirm the oxidative stress in the lungs, pulmonary contents of malondialdehyde (MDA) were measured. After instillation of the ETX in the lungs, lung leak index increased dramatically (p＜0.001), whereas mepacrine and ketotifen decreased the lung leak index significantly (p＜0.001). Lung PLA2 activity also increased (p＜0.001) after ETX treatment compared with control, which was reversed by mepacrine and ketotifen (p＜0.001). In the examination of expression of group I and II secretory PLA2, mRNA synthesis of the group II PLA2 was enhanced by ETX treatment, whereas ketotifen and WEB 2086, the PAF receptor antagonist, decreased the expression. The activity of the lysoPAF acetyltransferase increased (p＜0.001) after treatment of ETX, which implies the increased synthesis of PAF by the remodelling of lysoPAF in the lungs. Consequently, the contents of the PAF in the lungs were increased by ETX compared with control (p＜0.001), while mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the synthesis of the PAF in the lungs of ETX treated rats. The infiltration of the neutrophils was confirmed by measuring and enumerating lung MPO and the neutrophils in the BAL fluid respectively. Compared with control, ETX increased lung MPO and number of neutrophils in BAL significantly (p＜0.001) whereas mepacrine and ketotifen decrerased number of neutrophils (p＜0.001) and MPO (p＜0.05, p＜0.001, respectively). The lung MDA contents were also increased (p＜0.001) by ETX treatment, but treatment with mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the lung MDA contents. Collectively, we conclude that ETX increases PLA2 activity, and that the subsequently increased production of PAF was ensued by the remodelling of the lyso PAF resulting in tissue injury by means of oxidative stress in the lungs.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.479-491
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• 1998

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.84-101
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• 2010

Objectives : This study aimed to evaluate the protective effects of Seonpyejeongcheon-tang (SJT) on elastase-induced lung injury. Materials and Methods : The extract of SJT was treated to A549 cells and an elastase-induced lung injury mouse model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results : SJT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, protein level of cyclin B 1, Cdk1, and Erk1/2, and gene expression of TNF-$\alpha$ and IL-$1{\beta}$ in A549 cells. SJT treatment also revealed a protective effect on elastase-induced lung injury in mouse model. This effect was evidenced via histopathological findings, including immunofluoresence stains against elastin, collagen, and caspase 3, and protein levels of cyclin B1, Cdc2, and Erk1/2 in lung tissue. Conclusion : These data suggest that SJT has pharmaceutical properties on lung injury. This study thus provides scientific evidence for the efficacy of SJT for clinical application to patients with chronic obstructive pulmonary disease.

• Tuberculosis and Respiratory Diseases
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• v.68 no.6
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• pp.334-344
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• 2010

Background: Based on the known immunoregulatory functions of moxifloxacin on phagocytes, the therapeutic effect of moxifloxacin on oleic acid (OA)-induced acute lung injury (ALI) was investigated. Methods: Moxifloxacin (10 mg/kg) was given to male Sprague-Dawley rats that had been given oleic acid (OA, $30{\mu}L$) intravenously. Five hours after OA injection, parameters demonstrating ALI were assessed to measure the effects of moxifloxacin on acute lung injury. Results: The pathological findings of OA-induced ALI's was diminished by moxifloxacin. Through ultrastructural and $CeCl_3$ EM histochemistry, moxifloxacin was confirmed to be effective in decreasing oxidative stress in the lung as well. Indices of ALI, such as lung weight/body weight ratio, protein content in bronchoalveolar lavage fluid, and lung myeloperoxidase were decreased by moxifloxacin. In diaminobenzidine immunohistochemistry, fluorescent immunohistochemistry, and Western blotting of the lung, moxifloxacin had decreased the enhanced expression of secretory phospholipase $A_2$ ($sPLA_2$) by OA. Conclusion: We concluded that moxifloxacin was effective in lessening acute inflammatory pulmonary edema caused by OA, by inhibiting the neutrophilic respiratory burst, which was initiated by the activation of $sPLA_2$.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.522-531
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• 2003

Background : Hemorrhagic shock and trauma are two of the most common causes of acute lung injury. The activation of cyclooxygenase is one of the important causes of acute lung injury. This study investigated the effect of aspirin, a well-known cyclooxygenase inhibitor, on severe hemorrhage-induced acute lung injury in rats. Methods : The hemorrhagic shock was induced by withdrawing blood; 20ml/kg of B.W., through the femoral artery in 5 min. The mean arterial pressure was recorded through the femoral artery on a polygraph. Results : In the present investigation, the lung tissue myeloperoxidase activity, protein contents and leukocyte counts, in bronchoalveolar lavage fluid, increased significantly 2 and 24 h after the hemorrhage induction. Although the decreased mean arterial pressure spontaneously recovered, acute lung injury occurred after severe hemorrhage. These changes were effectively prevented by a single intravenous injection of aspirin (10 mg/kg of B.W.) 30 min before the hemorrhage. Conclusion : These results suggest that severe hemorrhage-induced acute lung injury is mediated, in part, by the activation of cyclooxygenase. Furthermore, pretreatment of aspirin in acute lung injury-prone patients, or prophylactic treatment of aspirin to the patients with precipitating conditions, could be helpful in the prevention of acute lung injury.

• Proceedings of the Korea Contents Association Conference
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• 2012.05a
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• pp.173-174
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• 2012

To determine whether position affects measured lung capacity of spinal cord injury patients. The study subjects were 45 patients with spinal cord injury (cervical level 15, thoracic level 15, lumbar level 15). Subjects were provided with a full explanation of the experimental procedures and all provided written consent signifying their voluntary participation. We used a spirometer (Spirometer, Micromedical Ltd, UK) to measure pulmonary function in the supine and sitting positions (straightened upper body at an angle of $90^{\circ}$). Forced vital capacity (FVC), forced expiratory volume during the first second (FEV1), tidal volume (TV), and maximum insufflation capacity (MIC) were also measured. FVC, FEV1, TV, MIC (%) were greater in the supine than in the sitting position for those with injury at the cervical or thoracic injury level. On the other hand, FVC, FEV1, TV, MIC (%) were lower in the supine position for those with an injury at the lumbar level. More attention should be paid to the effect of injury level on measured lung capacity.

• Preventive Nutrition and Food Science
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• v.9 no.1
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• pp.65-70
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• 2004

Side-stream cigarette smoke (SSCS) is a major component of environmental tobacco smoke. The purpose of this study was to investigate the development of lung injury and lipid peroxidation in the lung and liver of immunodeficient (Nude) mice exposed to acute SSCS (a total 5 hours of exposure). The effects of French maritime bark extract (Pycnogeno $l^{ⓡ}$) supplementation of the mice were also determined. SSCS increased pulmonary resistance and lipid peroxidation in these mice. Pycnogeno $l^{ⓡ}$ supplementation increased vitamin E levels in lung and liver. In addition, Pycnogeno $l^{ⓡ}$ attenuated SSCS-mediated lung injury and lipid peroxidation. It appears that the enhanced resistance against SSCS-induced lung injury and lipid peroxidation may be primarily due to the antioxidant property of Pycnogeno $l^{ⓡ}$ in supplemented mice.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.14.1-14.4
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• 2016

A total of 221 patients were evaluated to be humidifier disinfectant associated with lung injury (HDLI) through two rounds of programs through April 2015. The humidifier disinfectant (HD) brands most often associated with HDLI were found to be Oxy (n=151, 68 %) and Cefu (n=26, 17 %). Polyhexamethylene guanidine used for disinfectant for four types of HD brands including Oxy was found to be associated with the highest number of HDLI cases (n=188). Further programs are operating to identify various health effects including lung injury which may be associated with the use of HD. Not only national agencies, but also pertinent environmental health societies should cooperate in the necessary investigations so that this tragedy can be properly addressed and future incidents concerning chemicals and chemical-containing products can be prevented.

• Journal of Chest Surgery
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• v.32 no.11
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• pp.978-983
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• 1999

Background: Complement activation with transpulmonary leukocyte sequestration is considered a main mediator leading to ischemia-reperfusion lung(I-R) injury. We studied the role of leukocytes in the formation of I-R injury in ovine cardiopulmonary bypass(CPB) model with a membrane oxygenator. Material and Method: Five sheep were used. CPB circuitry consisted of a roller pump(American Optical Corp., Greenwich, CT, USA) and a membrane oxygenator(UNIVOX-IC, Bentley, Baxter Health Corp, Irvine, CA, USA). The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter a total CPB of 100 min was performed, followed by another 10 min of partial CPB. The CPB was discontinued and the animals were fully recovered. For measuring left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 min and 109 in after the start of CPB, and 30 min and 120 min after weaning. C3a was measured before thoracotomy, 109 min after the start of CPB, and 30 min and 120 min after weaning. Plasma malondialdehyde(MDA) was checked before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. One to two grams of lung tissue were taken for water content measurement before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. Lung biopsy specimens were examined by light and electron microscopy. Result: Of 5 animals, 4 survived the experimental procedures. Of these, 3 animals survived on a long-term basis. No significant differences in transpulmonary gradients of leukocyte were found and no significant complement activation was expressed by C3a levels. MDA level did not show significant changes related to lung reperfusion despite an increase after the start of CPB. On both light and electron microscopic examinations, mild to moderate acute lung change was observed. Interstitial edema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Conclusion: These findings indicate that ischemia-repersusion lung injury may not be from complement activation-leukocyte sequestration but from another source of oxygen free radicals related to CPB.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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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.