• 한국임상수의학회지
• /
• 제26권3호
• /
• pp.200-204
• /
• 2009

This study was performed to evaluate the effects of reduced L-glutathione on the oxidant/antioxidant status(superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GPx), protein carbonyl and lipid hydroperoxide(LPO) concentration), renal function(blood urea nitrogen(BUN) and serum creatinine levels), and microscopy of renal tissues in pigs undergoing unilateral renal ischemia-reperfusion(I/R). Sixteen Landrace and Yorkshire mixed-breed pigs were divided randomly into two groups: untreated control group and reduced L-glutathione-treated group(4 mg/kg IV). Each group had 8 pigs. Pigs were unilaterally nephrectomized and the kidney was subject to 30 min of renal pedicle occlusion. Blood samples for biochemical assay were collected on days 1, 3, 5, 7, and 14 post nephrectomy. Renal I/R injury were evaluated histopathologically by the microscopic observation of renal tissue sections and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as SOD, GPx, CAT, protein carbonyl and LPO were measured. The elevation of creatine and BUN levels was lower in the treated group, compared with the control group. The activities of antioxidant-enzyme were higher in the treated group, compared with the control group. In histological findings, the severity of damage in the reduced L-glutathione treated group was less when compared to the control group.

• Preventive Nutrition and Food Science
• /
• 제16권3호
• /
• pp.217-223
• /
• 2011

Ischemic stroke constitutes about 80% of all stroke incidences. It is characterized by brain cell death in a region where cerebral arteries supplying blood are occluded. Under these ischemic conditions, apoptosis is responsible for the cell death, at least in part. Goat's-beard (Aruncus dioicus var. kamtschaticus) is a perennial plant that grows naturally in the alpine regions of Korea. In the present study, we first determined whether water extract of goat's-beard (HY1646) and some of its fractions prepared by partitioning with organic solvents could improve the viability of human hepatocellular carcinoma cells (HepG2) cultured under hypoxic condition by blocking apoptotic pathways. Based on the in vitro findings, we subsequently investigated whether HY1646 and the ethyl acetate fraction (EA) selected from cell culture-based screening could attenuate brain injury in a rat middle cerebral artery occlusion (MCAO) model of ischemia (2 hr), followed by 22 hours of reperfusion. The cell number was sustained close to that initially plated in the presence of HY1646 even after 24 hr of cell culture under hypoxic condition (3% $O_2$), at which time the cell number reached almost zero in the absence of HY1646. This improvement in cell viability was attributed to the delay in apoptosis, identified by the formation of DNA ladder in gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA) and butanol, EA was chosen for the animal experiments because EA demonstrated the best cell viability at the lowest concentration (10 ${\mu}g$/mL). HY1646 (200 mg/kg) and EA (10 and 20 mg/kg) significantly reduced infarct size, an index of brain injury, by 16.6, 40.0 and 61.0%, respectively, as assessed by 2,3,5-triphenyl tetrazolium chloride staining. The findings suggest that prophylactic intake of goat's beard might be beneficial for preventing ischemic stroke.

• 한방재활의학과학회지
• /
• 제20권3호
• /
• pp.1-11
• /
• 2010

Objectives : This study was designed to investigate the effects of Lumbricus extract(LE) on the regional cerebral blood flow(rCBF) in ischemic rats, further to determine the mechanism of action of LE, and the effects that LE inhibits lactate dehydrogenase(LDH) activity in brain cells. Methods and materials : This study, ischemic rats were divided into total four group: control group(n=6), experimental group I (LE treated group)(n=6), experimental group II(LE treated group after pretreatment with indomethacin)(n=6), experimental group III(LE treated group after pretreatment with methylene blue)(n=6). And the measurement that LE inhibits LDH activity in the damage to brain cells to N-methyl-D-aspartic acid(NMDA). The changes of rCBF were determinated by laser-doppler flowmetry(LDF), and LDH activity was determinated by microplate reader in vitro. Results : 1. The rCBF was significantly improved by LE(10 mg/kg, i.p.) during the period of cerebral reperfusion, compared with the control group. 2. The rCBF was significantly increased by LE after pretreatment with indomethacin(1 mg/kg, i.p.), an inhibitor of cyclooxygenase, during the period of cerebral reperfusion, compared with the LE group, and rCBF was accelerated by LE after pretreatment with methylene blue($10{\mu}g/kg$, i.p.) an inhibitor of guanylate cyclase during the period of cerebral reperfusion, compared with the control group. 3. LE significantly inhibited LDH activity in vitro in a dose-dependent manner. Conclusions : From the above results, these were suggested that Lumbricus had anti-ischemia action in connection with cyclooxygenase and might prevent the brain cells death through inhibited LDH activity.

• Nutrition Research and Practice
• /
• 제13권3호
• /
• pp.205-213
• /
• 2019

BACKGROUND/OBJECTIVES: Myocardial infarction (MI) is caused by extensive myocardial damage attributed to the occlusion of coronary arteries. Our previous study in a rat model of ischemia/reperfusion (I/R) demonstrated that administration of arabinoxylan (AX), comprising arabinose and xylose, protects against myocardial injury. In this study, we undertook to investigate whether psyllium seed husk (PSH), a safe dietary fiber containing a high level of AX (> 50%), also imparts protection against myocardial injury in the same rat model. MATERIALS/METHODS: Rats were fed diets supplemented with PSH (1, 10, or 100 mg/kg/d) for 3 d. The rats were then subjected to 30 min ischemia through ligation of the left anterior descending coronary artery, followed by 3 h reperfusion through release of the ligation. The hearts were harvested and cut into four slices. To assess infarct size (IS), an index representing heart damage, the slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC). To elucidate underlying mechanisms, Western blotting was performed for the slices. RESULTS: Supplementation with 10 or 100 mg/kg/d of PSH significantly reduces the IS. PSH supplementation (100 mg/kg/d) tends to reduce caspase-3 generation and increase BCL-2/BAX ratio. PSH supplementation also upregulates the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and its target genes including antioxidant enzymes such as glutathione S-transferase mu 2 (GSTM2) and superoxide dismutase 2 (SOD2). PSH supplementation upregulates some sirtuins ($NAD^+$-dependent deacetylases) including SIRT5 (a mitochondrial sirtuin) and SIRT6 and SIRT7 (nuclear sirtuins). Finally, PSH supplementation upregulates the expression of protein kinase A (PKA), and increases phosphorylated cAMP response element-binding protein (CREB) (pCREB), a target protein of PKA. CONCLUSIONS: The results from this study indicate that PSH consumption reduces myocardial I/R injury in rats by inhibiting the apoptotic cascades through modulation of gene expression of several genes located upstream of apoptosis. Therefore, we believe that PSH can be developed as a functional food that would be beneficial in the prevention of MI.

• Journal of Ginseng Research
• /
• 제47권2호
• /
• pp.274-282
• /
• 2023

Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

• 대한한방내과학회지
• /
• 제43권6호
• /
• pp.1274-1288
• /
• 2022

Objectives: The study investigated the effect of Korean medicine treatment on a hemiplegic patient with conscious and cognitive disorders due to hemorrhagic transformation after interventional reperfusion therapy of anterior circulation infarction. Case presentation: The patient was treated with acupuncture, moxibustion, cupping, and herbal medicine in combination with Western medicine and physical therapy. The effects on clinical symptoms were evaluated using the Manual Muscle Test (MMT), Glasgow Coma Scale (GCS), Korean Mini-Mental State Examination (K-MMSE), Korean Nursing Delirium Screening Scale (Korean Nu-DESC), and Modified Bathel Index (MBI). After the treatment, the MMT grade increased from Gr.0-1 to Gr.0-3, the GCS score increased from 10 to 15, the K-MMSE score increased from 8 to 15, the Korean Nu-DESC score decreased from 3 to 1, night delirium disappeared, and the MBI score increased from 13 to 26. Conclusions: Complex Korean medicine treatments were effective for improving the clinical symptoms of hemorrhagic transformation after interventional reperfusion therapy for anterior circulation infarction in a patient with hemiplegia and conscious and cognitive disorders. However, further studies are needed.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권3호
• /
• pp.257-265
• /
• 2023

Kidney ischemia/reperfusion (I/R) injury, a common cause of acute kidney injury (AKI), is associated with the migration of inflammatory cells into the kidney. Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho family of small GTPase, plays an important role in inflammatory cell migration by cytoskeleton rearrangement. Here, we investigated the role of Rac1 on kidney I/R injury and macrophage migration. Male mice were subjected to either 25 min of bilateral ischemia followed by reperfusion (I/R) or a sham operation. Some mice were administrated with either NSC23766, an inhibitor of Rac1, or 0.9% NaCl (vehicle). Kidney damage and Rac1 activity and expression were measured. The migration and lamellipodia formation of RAW264.7 cells, mouse monocyte/macrophage, induced by monocyte chemoattractant protein-1 (MCP-1, a chemokine) were determined using transwell migration assay and phalloidin staining, respectively. In sham-operated kidneys, Rac1 was expressed in tubular cells and interstitial cells. In I/R-injured kidneys, Rac1 expression was decreased in tubule cells in correlation with the damage of tubular cells, whereas Rac1 expression increased in the interstitium in correlation with an increased population of F4/80 cells, monocytes/macrophages. I/R increased Rac1 activity without changing total Rac1 expression in the whole kidney lysates. NSC23766 administration blocked Rac1 activation and protected the kidney against I/R-induced kidney damage and interstitial F4/80 cell increase. NSC23766 suppressed monocyte MCP-1-induced lamellipodia and filopodia formation and migration of RAW 264.7 cells. These results indicate Rac1 inhibition protects the kidney against I/R via inhibition of monocytes/macrophages migration into the kidney.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2020년도 춘계학술대회
• /
• pp.76-76
• /
• 2020

Stachys sieboldii Miq. (chinese artichoke), which has been extensively used in oriental traditional medicine to treat of ischemic stroke; however, the role of Stachys sieboldii Miq. (SSM) in cerebral ischemia/reperfusion (I/R) injury is not yet fully understood. In the current study, the neuroblastoma cell line (SH-SY5Y) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury in vitro model. The results showed that SSM improved OGD/R-induced inhibitory effect on cell viability of SH-SY5Y Cells. SSM displayed anti-oxidative activity as proved by the decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in OGD/R-induced SH-SY5Y Cells. In addition, cell apoptosis was markedly decreased after SSM treatment in OGD/R-induced SH-SY5Y Cells. The up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, SSM protected human neuroblastoma SH-SY5Y cells from OGD/R-induced injury via preventing mitochondrial-dependent pathway through scavenging excessive ROS, suggesting that SSM might be a potential agent for the ischemic stroke therapy.

• Molecules and Cells
• /
• 제46권9호
• /
• pp.527-534
• /
• 2023

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been proposed but no definitive and effective therapies exist yet. This review summarizes the current update on the immune cell functions and discusses therapeutic potentials in liver IRI. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

• Journal of Chest Surgery
• /
• 제29권9호
• /
• pp.931-939
• /
• 1996

폐이식의 임상적용에 있어 공여폐의 기능보존 여부가 술후 경과에 결정적인 영향을 미치므로, 이식폐의 채취에서부터 이식까지의 기간동안의 적절한 보존 방법의 개발이 선행되어야되므로, 폐기능 보존에 적절한 용액의 조성을 알아보기위하여 이 실험을 시행하였다. 실험은 세포외액 조성인 Hartmann's solution에 보존한 군을 대조군(1군)으로 하고, 세포내액 조성 인 modified University of Wisconsin solution에 보존한 군(2군), 세포내액과 세포외액 중간형에 여러가지 substrates가 함유된 Kosin solution에 보존한 군(3군)으로 나누어 가토의 적출폐를 대상으로 시행하였다. 폐기능 보존효과를 비교하기 위하여 heart-lung blocs의 중량의 변화, 기도내압, 관류액내의 이산화탄소 분압의 변화를, 폐조직내의 lactate 및 adenosine deaminase의 수치를 측정하였고, 폐조직의 미세구조 변화를 관찰하여 다음과 같은 결과를 얻었다. 1. 재관류후 heart-lung bloc의 중량변화는 3군에서 가장 낮았다(P< .05). 2. 기도내압은 1군에서는 재관류후 증가되 었으나, 2, 3군에서는 감소되 었고, 특히 2군에서는 보존전의 기 도내압보다 더 낮았다. 3.재관류동안의 \ulcorner동맥압은 3군에서 가장 낮았고, 2군은 1군보다 더 높았다(P>0.1). 4. 폐조직내에서의 lactate와 ADA치는 3군이 1,2군보다 높았다(P< .05). 5. 관류액내의 이산화탄소 분압의 변화률은 3군이 1,2군보다 약간 높았다. 6.폐조직 미세구조의 변화는전반적얀 폐부종, 간질조직의 확장, 출혈 및 기저막의 이상소견을 보였으나 각 군간의 저명한 차이는 없었다. 결론적으로 modified University of Wisconsin solution과 Kosin solution의 폐기능 보존 효과는 Hartmann's solution 에 비하여 다소 우수한 것으로 생각된다.