• Proceedings of the PSK Conference
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• 2003.10b
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• pp.82.2-83
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• 2003

Beta-amyloid peptide (A${\beta}$) is considered to be responsible for the pathogenesis of the Alzheimer's disease. Several lines of evidence support that A${\beta}$-amyloid-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Agents that are able to scavenge excess ROS may be useful as protecting or reducing agents for development or progress of AD. Green tea extract has been known to have antioxidant property. Our previous studies also demonstrate that green tea extract protected ischemia/reperfusion-induced brain injury by reduction of cell death through scavenging of oxidative damages of macromolecules. (omitted)

• Journal of Veterinary Clinics
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• v.40 no.6
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• pp.423-428
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• 2023

The mouse kidney transplantation model serves as an invaluable tool for exploring various aspects of the transplant process, including acute rejection, cellular and humoral rejection, ischemia-reperfusion injury, and the evaluation of novel therapeutic strategies. However, conducting venous anastomosis in this model poses a significant challenge due to the thin and pliable characteristics of the renal vein, which often obstruct clear visualization of the resected vein's edge. This study proposes the adoption of a two stay suture technique to enhance the visualization of the renal vein's edge, thereby facilitating efficient and successful venous anastomosis. A total of 22 mice served as kidney donors in this study. The conventional anchoring suture technique was employed for venous anastomosis in 11 of these mice, while the remaining 11 underwent the two stay suture technique. The anastomosis duration and completion rates were then compared between these two groups. The conventional anchoring suture technique yielded an average anastomosis time of 29 minutes and a completion rate of 64%. In contrast, the two stay suture technique demonstrated a substantial improvement, with an average anastomosis time of 14 minutes and a completion rate of 100%. The two stay suture technique offers a promising solution to enhance visualization during venous anastomosis in murine kidney transplantation. This technique may particularly benefit novices by enabling them to perform venous anastomosis more easily, swiftly, and successfully.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2004.04a
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• pp.3-10
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• 2004

Oxidative stress is a constant threat to all living organisms and an immense repertoire of cellular defense systems is being employed by most pro- and eukaryotic systems to eliminate or to attenuate oxidative stress. Ischemia and reperfusion is characterized by both a significant oxidative stress and characteristic changes in the antioxidant defense. Heme oxigenase-l (HO-l) is up-regulated by various stimuli including oxidative stress so that it is thought to participate in general cellular defense mechanisms against ischemic injury in mammalian cells. Higenamine, an active ingredient of Aconite tuber, has been shown to have antioxidant activity along with inhibitory action of inducible nitric oxide synthase (iNOS) expression in various cells. In the present study, we investigated whether higenamine and related analogs protect cells from oxidative cellular injuries by modulating antioxidant enzymes, such as HO-l, MnSOD etc. R-form of YS-51 was the most potent inducer of HO-l in bovine endothelial cells, which inhibited apoptotic cell death by H$_2$O$_2$. HO-1 induction by YS 51 was mediated by PI3 kinase activation in which PKA- as well as PKG pathway is considered as important regulators. YS-51 also induced Mn-SOD mRNA expression by activating c-jun N-terminal kinase in endothelial cells and Hela cells. In ROS 17/2.1 cells, higenamine and enetiomers of related compounds inhibited iNOS expression by cytokine mixtures. Taken together, higenamine and related compounds can be developed as possible protective agents from oxidative cell injury or death.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.160-166
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• 2000

The present study examined influence of various ischemic duration on extent of focal ischemic brain injury induced by middle cerebral artery occlusion (MCAO) in rats. The MCAO was produced by insertion of a 17 mm silicone-coated 4-0 nylon surgical thread to the origin of MCA through the internal carotid artery for 30, 60, 90, 120 min (transient) or 24 hr (permanent) in male Sprague-Dawley rats under isoflurane anesthesia. Reperfusion in transient MCAO models was achieved by pulling the thread out of the internal carotid artery. Only rats showing neurological deficits characterized by left hemiparesis and/or circling to the left, were included in cerebral ischemic groups. The rats were sacrificed 24 hr after MCAO and seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride. Infarct size was measured using a computerized image analyzer. Ischemic damage was common in the frontoparietal cortex (somatosensory area) and the lateral segment of the striatum while damage to the medial segment of the striatum depended on the duration of the occlusion. In the 30-min MCAO grouts, however, infarcted region was primarily confined to the striatum and it was difficult to clearly delineate the region since there was mixed population of live and dead cells in the nucleus. Infarct volume was generally increased depending on the duration of MCAO, showing the most severe damage in the permanent MCAO group. However, there was no significant difference in infarct size between the 90-min and 120-min MCAO groups. % Edema also tended to increase depending on the duration of MCAO. The results suggest that the various focal ischemic rat models established in the present study can be used to evaluate in vivo neuroprotective activities of candidate compounds or to elucidate pathophysiological mechanisms of ischemic neuronal cell death.

• Journal of Chest Surgery
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• v.47 no.3
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• pp.233-239
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• 2014

Background: As hypertrophied myocardium predisposes the patient to decreased tolerance to ischemia and increased reperfusion injury, myocardial protection is of utmost importance in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis (AS). Methods: Consecutive 314 patients (mean age, $62.5{\pm}10.8$ years; 143 females) with severe AS undergoing isolated AVR were included. Postoperative myocardial injury (PMI) was defined as 1) maximum postoperative creatinine kinase isoenzyme MB or troponin-I levels ${\geq}10$ times of reference, 2) postoperative low cardiac output syndrome or episodes of ventricular arrhythmia, or 3) left ventricular ejection fraction of less than 55% and decrease in left ventricle (LV) ejection fraction of more than 20% of the baseline value. Results: There were 90 patients (28.7%) who developed PMI. There were five cases of early death (1.6%), all of whom had PMI. On multivariable analysis, the use of histidine-tryptophan-ketoglutarate (HTK) solution instead of blood cardioplegia (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.63 to 5.77; p=0.001), greater LV mass (OR, 1.04; 95% CI, 1.01 to 1.07; p=0.007), and increased cardiac ischemic time (OR, 1.13; 95% CI, 1.05 to 1.22; p<0.001) were independent predictors for PMI. Patients who had PMI showed significantly inferior long-term survival than those without PMI (p=0.049). Conclusion: PMI occurred in a considerable proportion of patients undergoing AVR for severe AS and was associated with poor long-term survival. HTK cardioplegia, higher LV mass, and longer cardiac ischemic duration were suggested as predictors of myocardial injury.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.207-211
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• 2004

The purpose of the present study was to evaluate the expression of cardiac marker protein in rabbit cardiac tissue that was exposed to ischemic preconditioning (IPC), or ischemiareperfusion injury (IR) using two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). We compared 2DE gels of control (uninjured) cardiac tissue with those of IPC and IR cardiac tissue. Expression of one protein was detected in IR heart tissue, however the protein was not detected in the samples of control and IPC tissue. To further characterize the detected protein molecule, the protein in the 2D gel was isolated and subjected to trypsin digestion, followed by MALDI-MS. The protein was identified as myoglobin, which was confirmed also by Western blot analysis. These results are consistent with previous studies of cardiac markers in ischemic hearts, indicating myoglobin as a suitable marker of myocardial injury. In addition, the present use of multiple techniques indicates that proteomic analysis is an appropriate means to identify cardiac markers in studies of IPC and IR.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.317-325
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• 2006

Purpose : This study was carried out to elucidate the effects of nitric oxide synthase(NOS) inhibitor, NG-monomethyl-L-arginine(L-NMMA) and nitric oxide precursor, L-arginine(L-Arg) on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion(RR) after hypoxia-ischemia(HI) in newborn piglets. Methods : Twenty-eight newborn piglets were divided into 4 groups; Sham normal control(NC), experimental control(EC), L-NMMA(HI & RR with L-NMMA), and L-Arg(HI & RR with L-Arg) groups. HI was induced by occlusion of bilateral common carotid arteries and simultaneously breathing with 8 percent oxygen for 30 mins, and followed RR by release of carotid occlusion and normoxic ventilation for one hour. All groups were monitored with cerebral hemodynamics and cytochrome $aa_3$ (Cyt $aa_3$) using near infrared spectroscopy(NIRS). $Na^+$, $K^+$-ATPase activity, lipid peroxidation products, and tissue high energy phosphate levels were determined biochemically in the cerebral cortex. Results : In experimental groups, mean arterial blood pressure, $PaO_2$, and pH decreased, and base excess and blood lactate level increased after HI compared to NC group(P<0.05). These variables subsequently returned to baseline after RR except pH. There were no differences among the experimental groups. In NIRS, oxidized hemoglobin($HbO_2$) decreased and hemoglobin(Hb) increased during HI(P<0.05) but returned to base line immediately after RR; 40 min after RR, the $HbO_2$ had decreased significantly compared to NC group(P<0.05). Changes of Cyt $aa_3$ decreased significantly compared to NC after HI and recovered at the end of the experiment. Significantly reduced cerebral cortical cell membrane $Na^+$, $K^+$-ATPase activity and increased lipid peroxidation products(P<0.05) were not improved with L-NMMA or L-Arg. Conclusion : These findings suggest that NO is not involved in the mechanism of HI and RR brain damage during the early acute phase of RR.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.95-100
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• 2004

Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

• Biomolecules & Therapeutics
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• v.7 no.4
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• pp.362-370
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• 1999

Propolis, a natural resinous compound collected from honey bees, contains many biochemical constituents(wax, flavonoids, phenolic compounds, etc.) and has been used in traditional medicines as early as 300 B.C. It was been demonstrated that ethanol, acetylsalicylic acid, ischemia reperfusion, non-steroidal antiin-flammatory drugs and stress induce gastric lesions by promoting the generation of reactive oxygen metabolites. Therefore, some drugs that are capable of scavenging or inhibiting the generation of reactive oxygen radicals might be expected to prevent the gastric mucosal injury. The aim of this study was 1) to examine the antiulcer effect of propolis, 2) to investigate the mechanism of action by determining gastric acid secretion, lipid per-oxidation, mucus content and proton pump ($H^+$/$K^+$-ATPase) activity on gastric mucus in varios experimental models, and finally, 3) to isolate and identify the pure compounds that exert antiulcer activity. Step 2-1 and 2-3 sub-sub fraction shoed a significant reduction of severity of gastirc damage at the dose of 25 mg/kg in various experimental models. We isolated 4 sub-sub-sub fractions by flash column chromatography of Step 2-1 sub-sub fraction and one sub-sub-sub fraction by recrystalization of Step 2-3 sub-sub fraction. The protective effects of propolis sub-sub-sub fraction manifested sifnificant effects in HCl-ethanol induced gastric erosion model and aspirin induced gastric ulcer model. These results showed that the gastric mucosal protective effect of propolis might result from the increase of mucus secretion, free radical scavenging effect as well as the reduction of acid secretion in accordance with the reduction of $H^+$/$K^+$-ATPase activitv. Three compounds were isolated and identified from sub-sub fraction of propolis which showed antiulcer effects. Subsequently, these compounds were identified as a flavonoid, namely, 2-acetoxy-5,7,-dihydroxy-flavanone, galangin and chrysin.

• Molecules and Cells
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• v.40 no.11
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• pp.837-846
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• 2017

As a component of the neurovascular unit, cerebral smooth muscle cells (CSMCs) are an important mediator in the development of cerebral vascular diseases such as stroke. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acid catalyzed by cytochrome P450 epoxygenase. EETs are shown to exert neuroprotective effects. In this article, the role of EET in the growth and apoptosis of CSMCs and the underlying mechanisms under oxygen glucose deprivation (OGD) conditions were addressed. The viability of CMSCs was decreased significantly in the OGD group, while different subtypes of EETs, especially 14,15-EET, could increase the viability of CSMCs under OGD conditions. RAPA (serine/threonine kinase Mammalian Target of Rapamycin), a specific mTOR inhibitor, could elevate the level of oxygen free radicals in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. However, SP600125, a specific JNK (c-Jun N-terminal protein kinase) pathway inhibitor, could attenuate oxygen free radicals levels in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. These results strongly suggest that EETs exert protective functions during the growth and apoptosis of CSMCs, via the JNK/c-Jun and mTOR signaling pathways in vitro. We are the first to disclose the beneficial roles and underlying mechanism of 14,15-EET in CSMC under OGD conditions.