• 대한임상독성학회지
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• 제18권1호
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• pp.34-41
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• 2020

Purpose: This study evaluated aggressive hyperbaric oxygen therapy (HBOT) by understanding various exposure routes of acute carbon monoxide (CO) poisoning, the risk factors causing acute cardiovascular, and neurological toxicity caused by poisoning. Methods: A retrospective study was conducted based on the medical records of 417 acute CO poisoning patients who visited the emergency care unit from March 2017 to August 2019. The exposure routes, HBOT performance, age, sex, medical history (hypertension, diabetes mellitus, ischemic heart disease, heart failure), intentionality, loss of consciousness (LOC), intake with alcohol or sedatives, and initial test results (carboxyhemoglobin (COHb), troponin-I, electrocardiography, echocardiography, brain MRI) were examined. Comparative analysis of the clinical information was conducted between the groups that showed acute cardiovascular toxicity and neurological toxicity, and groups that did not. Results: Among 417 patients diagnosed with acute CO poisoning, 201 cases (48.2%) were intentional, and charcoal briquette was the most common route (169 patients (40.5%)). Two hundred sixteen cases (51.8%) were accidental, and fire was the most common route (135 patients (32.4%)). The exposure route was more diverse with accidental poisoning. Three hundred ninety-nine patients were studied for acute cardiovascular toxicity, and 62 patients (15.5%) were confirmed to be positive. The result was statistically significant in intentionality, LOC, combined sedatives, initial COHb, HTN, and IHD. One hundred two patients were studied for acute neurological toxicity, which was observed in 26 patients (25.5%). The result was statistically significant in age and LOC. Conclusion: Active HBOT should be performed to minimize damage to the major organs by identifying the various exposure routes of CO poisoning, risk factors for acute cardiovascular toxicity (intentionality, LOC, combined sedatives, initial COHb, HTN, IHD), and the risk factors for acute neurological toxicity (age, LOC).

• 대한한방내과학회지
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• 제41권1호
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• pp.44-58
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• 2020

Objectives: This study was conducted to identify the protective effects of Chongmyunggongjin-dan (CMGJD) on Hydrogen peroxide (H₂O₂)-induced apoptosis mechanisms in C6 glial cells. Method: We used CMGJD after distilled water extraction, filtration, and lyophilization. The ROS scavenging effect was examined by fluorescence microscopy. Expression levels of proteins related to ROS generation were investigated by western blotting. Functional changes in organelles related to Reactive oxygen species (ROS) generation were investigated by immunoblotting and by verifying expression level of relevant enzymes. Results: The CMGJD extract protected the cells against H₂O₂-induced morphological changes and DNA fragmentation, inhibited the increase of Heme_oxygenase-1(HO^-1) and the decrease in catalase, protected against the loss of mitochondrial membrane potential, inhibited disturbances of lysosomal function, and induced an increase in peroxisomes. Conclusion: CMGJD was confirmed to have a protective effect on H₂O₂-induced C6 glial cell death possibly by blocking the pathways causing damage to subcellular organelles, such as mitochondria, lysosomes, and peroxisomes. We assume that CMGJD will be effective for the prevention and treatment of ischemic stroke in a clinical environment.

• 대한한의학회지
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• 제24권2호
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• pp.179-192
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• 2003

Objectives : Boyanghwanoh-tang (Buyanhaiwu-tang) has been used as a prescription for stroke, senile and vascular dementia, ischemic brain and heart damage in Oriental traditional medicine. However, there is little known about the mechanism by which the water extracts of Boyanghwanoh-tang (Buyanhaiwu-tang) rescue cells fromthese damages, and little is known about the protective mechanisms of Boyanghwanoh-tang (Buyanhaiwu-tang) on oxidative stress in neuronal cells. Therefore, we have investigated the role of Boyanghwanoh-tang (Buyanhaiwu-tang) on serum and glucose deprived apoptosis in PC12 cells. Methods : PC12 Cells have been used extensively as a model for studying the cellular and molecular effects of neuronal cells. The viability of cells was measured by MIT assay. We used DNA fragmentation and caspase 1, 2, 3, 6, 9-likeproteases activation assay. Transcriptional activation of NF-kB was assessed by using electrophoretic mobility shift assay. Results : Boyanghwanoh-tang (Buyanhaiwu-tang) rescued PC12 cells from apoptotic death by serum and glucose deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Boyanghwanoh-tang (Buyanhaiwu-tang) attenuated nuclear condensation and fragmentation, which represent typical neuronal apoptotic characteristics. Boyanghwanoh-tang (Buyanhaiwu-tang) also prevents fragmentation of genomic DNA and activation of caspase 3-like protease in serum and glucose deprived PC12 cells. Furthermore, Boyanghwanoh-tang (Buyanhaiwu-tang) reduced the activation of NF-kB by serum and glucose-deprived apoptosis. Conclusions : These findings suggest that serum and glucose deprivation induces reduced glutathione (GSH) depletion, and consequently, apoptosis through endogenously produced reactive oxygen species in PC12 cells. Also, our data indicated that Boyanghwanoh-tang (Buyanhaiwu-tang) has protective effects against the serum and glucose deprived deaths of PC12 cells, which are mediated by the generation of GSH that, in turn, can reduce oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide.

• Environmental Analysis Health and Toxicology
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• 제21권1호
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• pp.71-79
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• 2006

Epidemiologic studies have showed a close correlation between arsenic exposure and heart disease such as, cardiovascular problem, ischemic heart disease, infarction, atherosclerosis and hypertension in human. It may increase the mortality of high risk group with heart disease. Regarding the mechanism studies of heart failure, blood vessel, vascular smooth muscle cells and endothelial cells have long been focused as the primary targets in arsenic exposure but there are only a few studies on the cardiomyocytes. In this study, the generation of oxidative stress by low dose of arsenic trioxide was investigated in rat cardiomyocytes. By direct measurement of reactive oxygen species and fluorescent microscopic observation using fluorescent dye 2',7'-dichlorofluorescin diacetate, reactive oxygen species were found to be generated without cell death, where cells are treated with 0.1 ppm arsenic for 24 hours. With the induction of reactive oxygen species, GSH level was decreased by the same treatment. However, DNA damage did not seem to be serious by DAPI staining, while high dose of arsenic (2 ppm for 24 hrs) caused fragmentation of DNA. To identify the molecular biomarkers of low-dose arsenic exposure, gene expression was also investigated with whole genome microarray. As results, 9,022 genes were up-regulated including heme oxygenase-l and glutathione S-transrerase, which are well-known biomarkers of oxidative stress. 9,404 genes were down-regulated including endothelial type gp 91-phox gene by the treatment of 0.1 ppm arsenic for 24 hours. This means that biological responses of cardiomyocytes may be altered by ROS induced by low level arsenic without cell death, and this alteration may be detected clearly by molecular biomarkers such as heme oxygenase-1.

• Journal of Chest Surgery
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• 제33권2호
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• pp.125-131
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• 2000

Background: Hyperinflation during lung ischemia has been known to improve pulmonary functions after reperfusion which may be exerted through a pulmonary vasodilation and avoidance of atelectasis by an increased surfactant release and been known whether the improvement of pulmonary function was the effect of hyperinflation itself or the oxygen content in inflation gas. Therefore we attempted to clarify the effect of hyperinflation with oxygen in pulmonary inflation gas during warm ischemia on pulmonary function after reperfusion to solve the problem of ischemia-reperfusion injury after lung transplantation. Material and Method: sixteen mongrel dogs were randomly divided into two groups: the left lung was inflated to 30-35 cm H2O with 100% oxygen in oxygen group and 100% nitrogen in nitrogen group. The inflated left lung was maintained with warm ischemia for 100 minutes. Arterial and mixed venous blood gas analysis and hemodynamics were measured before ischemia and 30, 60, 120, 180 and 240 minutes afer reperfusion. Lung biopsy was taken for the measurement of lung water content after the end of reperfusion. Result: In oxygen group arterial oxygen tension the difference of arterial and mixed venous oxygen tension and the difference of alveolar-arterial oxygen tension at 30-minute after reperfusion were not significantly different from those before ischemia and were stable during the 40hour reperfusion. However in nitrogen group these values were significantly deteriorated at 30-minute after reperfusion. there was no significant difference between two groups in hemodynamic data peak airway pressure and lung water content. Conclusion : The results indicated that the oxygenation one of the most important pulmonary functions was improved by pulmonary inflation with 100% oxygen during warm ischemia but the hemodynamics were not. Oxygen as a metabolic substrate during warm ischenia was believed to make the pulmonary tissues to maintain aerobic metabolism and to prevent ischemic damage of alveoli and pulmonary capillary.

• Journal of Chest Surgery
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• 제27권5호
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• pp.345-352
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• 1994

We have performed left lung transplantation followed by ligation of right pulmonary artery in 14 dogs at the Chest Disease Research Institute, Yonsei University College of Medicine from May 1992 to February 1994. Excised left lung was perfused with 1500cc of 4$^{\circ}$C cold Euro-Collin`s[E-C] solution at a pressure of 30cmH2O through main pulmonary artery and preserved in 4$^{\circ}$C cold E-C solution for one hour. Left lung transplantation were proceeded in order of left atrium, left main bronchus, left pulmonary artery and right pulmonary artery ligation as usual method. The femoral artery and pulmonary artery pressures were monitored for more than 5 hours after the transplantations in 14 dogs. Six recipient dogs had elevated mean pulmonary artery pressure to greater than 30mmHg after the left lung transplantation and ligation of right pulmonary artery. The cause of elevated mean pulmonary artery pressure was due to inadequate preservation resulting in ischemic damage to donor lungs in 3 cases, and inadequate surgical techniques in 3 cases. Two recipient dogs without surgical complications died immediate post-operatively due to hemorrhagic shock. The bleeding focuses were LA anastomotic site in one case and femoral artery puncture site in another case. The remaining 6 recipient dogs showed mean pulmonary arterial pressure less than 30mmHg. However, one dog had spontaneous pneumothorax in post-operative 4 days, and another dog had rejection phenomenon in post-operative 5 days which was confirmed by pathologic findings of extracted transplanted lung. One dog succumbed of severe hemoptysis which was due to lung abscess with pin point stenosis of bronchial anastomosis in post-operative 38 days. In conclusion, elevated mean pulmonary arterial pressure greater than 30mmHg in immediate postoperative period can be due to inadequate preservation of extracted lung or poor surgical techniques. And the two dogs succumbed of hemorrhagic shock even though the mean pulmonary arterial pressure was less than 30mmHg. It is thought that careful preservation of the extracted donor lung in 4oC E-C solution and complete surgical techniques are the most important factors early and late complications.

• 사상체질의학회지
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• 제26권2호
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• pp.165-179
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• 2014

Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• BMB Reports
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• 제52권7호
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• pp.439-444
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• 2019

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer's disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced ${\beta}$-amyloid ($A{\beta}$) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced $A{\beta}$ production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin $E_2$, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced $A{\beta}$ production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity.

• 대한본초학회지
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• 제35권1호
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• pp.1-8
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• 2020

Objectives : This study was conducted to evaluate the effects of Corni Fructus, the dried fruits of Cornus officinalis Sieb., on unilateral common carotid artery occlusion (UCCAO) in mouse model. Methods : The Corni Fructus used in the experiment was extracted with anhydrous methanol, then filtered and freeze-dried. C57BL/6 mice used in the experiments were conducted left UCCAO surgery to set up UCCAO rodent model for mice. The mice were divided into five groups for evaluate the effect of methanol extract of Corni Fructus (COM) on UCCAO induced ischemic brain injury. The expression levels of nitric oxide in cerebrum and serum, body weight change were measured. To determine the effect of UCCAO and COM administration on brain neurons, morphological changes of the cerebrum through a microscope was conducted. And western blot was performed to confirm the underlying mechanism of neuroprotective effect of COM administration. Results : COM administered UCCAO groups (CO50, CO150, and CO500) had no significant effects on nitric oxide production in ipsilateral hemisphere proteins and sera. The CO500, 500 mg/kg COM administration, attenuated UCCAO-induced p38 inflammatory signaling pathway and inflammatory mediators such as iNOS and COX-2. The CO500 group showed resilient morphological changes of hippocampus neuronal cells about brain damage caused by decreased flow of blood. These group also showed decreased inflammation and cellular stress response in neuronal cells. Conclusions : From these results, COM has a neuroprotective property via moderating inflammatory factors and cellular stress inducing factors in brain cells.