• Archives of Reconstructive Microsurgery
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• v.9 no.2
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• pp.190-198
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• 2000

본 연구는 백서 복직근피판에 있어 허혈-재혈류 손상에 미치는 prostaglandin E1(PGE-1)의 예방효과를 분석 실험하였으며, 그 기전으로 내피세포의 intercellular adhesion molecule-1(ICAM-1)이 down regulation 됨을 확인하였다. 기존의 PGE-1은 혈관 확장 및 혈소판 응고 저하 등의 기전으로 피판 이식술 후 주로 사용하였으나, 허혈-재혈류 손상 시에 PGE-1 역할에 대한 연구는 잘 알려진바 없다. 허혈-재혈류 손상에 대한 기전은 현재 여러 가설로 설명되고 있으나, 최근 내피 세포와 백혈구의 역할이 주목을 받고 있다. 장시간 허혈 상태의 피판은 재혈류시 백혈구가 내피세포에 접착함으로써 직간접적인 경로로 독소를 생성하며, 결국 내피세포 및 주변조직의 괴사로 이어진다. 본 연구는 면역조직학 염색을 통한 내피세포의 ICAM-1 발현 억제와 그로 인한 백혈구의 내피세포 접착 억제를 그 기전으로 볼 수 있었으며, PGE-1을 술 중 투여함으로써 피판의 생존율을 향상시킬 수 있었다.

• Biomedical Science Letters
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• v.11 no.4
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• pp.441-446
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• 2005

The molecular mechanism of ischemia/reperfusion injury remains unclear. Reactive oxygen species (ROS) are implicated in cell death caused by ischemia/reperfusion in vivo or hypoxia in vitro. Poly (ADP-ribose) polymerase (PARP) activation has been reported to be involved in hydrogen peroxide-induced cell death in renal epithelial cells. This study was therefore undertaken to evaluate the role of P ARP activation in chemical hypoxia in opossum kidney (OK) cells. Chemical hypoxia was induced by incubating cells with antimycin A, an inhibitor of mitochondrial electron transport. Exposure of OK cells to chemical hypoxia resulted in a time-dependent cell death. In OK cells subjected to chemical hypoxia, the generation of ROS was increased, and this increase was prevented by the $H_2O_2$ scavenger catalase. Chemical hypoxia increased P ARP activity and chemical hypoxia-induced cell death was prevented by the inhibitor of PARP activation 3-aminobenzamide. Catalase prevented OK cell death induced by chemical hypoxia. $H_2O_2$ caused PARP activation and $H_2O_2-induced$ cell death was prevented by 3-aminobenzamide. Taken together, these results indicate that chemical hypoxia-induced cell injury is mediated by PARP activation through H202 generation in renal epithelial cells.

• The Journal of Internal Korean Medicine
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• v.26 no.3
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• pp.596-604
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• 2005

Objectives : Geopungjeseub-tang(Gufengchushi-tang) has been used in oriental medicine for many centuries as a therapeutic agent for hemiplegia caused by deficiency of qi(氣虛) and damp phlegm(濕痰). This study was performed to evaluate effects of Geopungjeseub-tang extract(GJT) on hemodynamics[regional cerebral blood flow(rCBF), pial arterial diameter(PAD), mean arterial blood pressure(MABP), heart rate(HR)] in normal rats and in rats with cerebral ischemia by middle cerebral artery(MCA) occlusion. Also, effects of adrenergic ${\beta}-receptor$, cyclooxygenase on response to GJT were evaluated. Methods : Laser-doppler flowmetry(LDF) measured changes of rCBF, MABP and HR. Video microscope and width analyzer measured changes in PAD. Results : rCBF and PAD increased after treatment with GJT(10mg/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with indomethacin raised rCBF and PAD increased after treatment with GJT during the same period as above. Pretreatment with propranolol decreased rCBF, but increased after GJT treatment, but raised PAD increased after GJT treatment during this period of reperfusion. Conclusion : CR caused diverse responses were observed in rCBF and PAD after treatment with GJT. ACF action is mediated by adrenergic ${\beta}-receptor$ and cyclooxygenase. Result suggest that GJT has an anti-ischemic effect through the improvement of cerebral hemodynamics and has theraputic potential for cerebral apoplexy.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1136-1140
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• 2004

Red ginseng and fermented red ginseng were prepared, and their composition of ginsenosides and antiischemic effect were investigated. When ginseng was steamed at 98-$100{\circ}C$ for 4h and dried for 5h at $60{\circ}C$, and extracted with alcohol, its main components were ginsenoside $Rg_3$ > ginsenoside $Rg_1$> ginsenoside $Rg_2$. When the ginseng was suspended in water and fermented for 5 days by previously cultured Bifidobacterium H-1 and freeze-dried (fermented red ginseng), its main components were compound K > ginsenoside $Rg_3{\geq}$ ginsenoside $Rg_2$. Orally administered red ginseng extract did not protect ischemia-reperfusion brain injury. However, fermented red ginseng significantly protected ischemica-reperfusion brain injury. These results suggest that ginsenoside Rh2 and compound K, which was found to be at a higher content in fermented red ginseng than red ginseng, may improve ischemic brain injury.

• The Korean Journal of Food & Health Convergence
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• v.5 no.4
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• pp.25-28
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• 2019

Now a days problem in health has become common. So, instead of curing them, prevention through dietary supplements has proven to be useful. In the case of patients who have already developed the disease atleast relieving pain and suffer is a challenging thing. In this context L- arginine is doing better compared to other essential aminoacids up to some extent. Arginine was found to reduce the pain associated with pulmonary hypertension foun to be associated with sickle cell anaemia. It also reduces the reperfusion injury after ischemia, trauma and shock. Some of the drugs with L-arginine as component are under clinical trials and hope to be available in the market soon. Severe preeclampsia is characterised by headaches, blurred vision, and inability to have high photovision, nausea and vomiting. L-Arginine along with Vit C and E are given as medical food to the patients and decrease in condition symptoms is the project now under phase II clinical trial. However the role of arginine in ameolirating preeclampsia symptoms is uncertain except with that of hypertension. Arginine is used to treat pain in sickle cell anaemia, lung damage, reperfusion injury, Trauma and shock but should be excluded during sepsis.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.664-668
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• 2002

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

• Molecules and Cells
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• v.40 no.8
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• pp.542-549
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• 2017

Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.225-234
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• 2018

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.475-485
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• 2017

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.218-223
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• 2008

Oxidative stress is believed to contribute to the neuronal damage induced by cerebral ischemia/reperfusion injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of hydroxyfullerene (a radical absorbing cage molecule) against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Wistar rats by four vessel- occlusion (4VO) for 10 min. Lipid peroxidation in brain tissues was determined by measuring the concentrations of thiobarbituric acid-reactive substances (TBARS). Furthermore, the apoptotic effects of ${H_2}{O_2}$ on PC12 cells were also investigated. Cell viabilities were measured using MTT [3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide] assays. Hydroxyfullerene, when administered to rats at 0.3-3 mg/kg i.p. at 0 and 90 minutes after 4-VO was found to significantly reduce CA1 neuron death by 72.4% on hippocampal CA1 neurons. Our findings suggest that hydroxyfullerene protects neurons from transient global cerebral injury in the rat hippocampus by reducing oxidative stress and lipid peroxidation levels, which contribute to apoptotic cell death.