• The Korean Journal of Physiology and Pharmacology
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• 제21권5호
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• pp.457-464
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• 2017

Etoricoxib features antioxidant and anti-inflammatory properties concomitantly, suggesting that it may be beneficial in testicular ischemia reperfusion (I/R) damage. Our aim is to investigate the effects of etoricoxib on testicular I/R damage induced with torsion-detorsion (TD). The etoricoxib + torsion-detorsion (ETD) groups of animals were given etoricoxib in 50 and 100 mg/kg of body weight (ETD-50 and ETD-100), while the testes torsion-detorsion (TTD) and sham operation rat group (SOG) animals were given single oral doses of distilled water as a solvent. TTD, ETD-50 and ETD-100 groups were subjected to $720^{\circ}$ degrees torsion for four hours, and detorsion for four hours. The SOG group was not subjected to this procedure. Biochemical, gene expression and histopathological analyses were carried out on the testicular tissues. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta ($IL-1{\beta}$) and tumor necrosis factor alpha ($TNF-{\alpha}$) were significantly higher, and the levels of total glutathione (tGSH) and glutathione reductase (GSHRd) were significantly lower in the TTD group, compared to the ETD-50, ETD-100 and SOG groups. Etoricoxib at a dose of 100 mg/kg better prevented I/R damage than the 50 mg/kg dose. Etoricoxib may be useful in clinical practice in the reduction of I/R damage on testes caused by torsion-detorsion.

• Journal of Korean Neurosurgical Society
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• 제57권5호
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• pp.335-341
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• 2015

Objective : The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuro-protective effects of kefir on spinal cord ischemia injury in rats. Methods : Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results : The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-$1{\alpha}$ and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion : Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.283-289
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• 2013

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/$dt_{max}$) and maximal rate of relaxation (-dP/$dt_{max}$). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

• Preventive Nutrition and Food Science
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• 제6권1호
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• pp.43-50
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• 2001

The effects of cardiac ischemia-reperfusion and $\beta$-adrenergic stimulation on metabolic function and energetics were investigated in Lan gendorff-perfused spontaneously hypertensive rat (SHR) hearts. Sarcoplasmic reticulum {TEX}$Ca^{2+}${/TEX}-dependent ATPase and cardiac lactate dehydrogenase (LDH) are additionally studied. The perfusion medium (1.0 mM {TEX}$Ca^{2+}${/TEX}) contained 5 mM glucose(+5 U/L insulin) and 2 mM pyruvate as substrates. Global ischemia was induced by reducing perfusion pressure of 100 to 40 cm {TEX}$H_{2}${/TEX}O, followed by 20 min reperfusin. Isoproterenol (ISO, 1$\mu$M) was infused for 10 min. Coronary vascular resistance and myocardial oxygen consumption ({TEX}$MVO_{2}${/TEX}) of SHR were increased in parallel with enhanced venous lactate during ischemia and reperfusion compared to those of Sprague Dawley (SD) hearts. Although ischemia-induced increase in venous lactate and combined adenosine plus inosine was abolished, coronary vasodilation produced in SD during reperfusion. In SHR, depressed reactive hyperemia was associated with a fall in cardiac ATP and CrP/Pi ratio and a rise in intracellular lactate/Pyruvate ratio. On the other hand, ISO produced coronary functional hyperemia and an increase in {TEX}$MVO_{2}${/TEX}. However, these responses were less than those in SHR hearts. The ATPase activity of SHR was attenuated in free {TEX}$Ca^{2+}${/TEX} concentrations used under basal condition and with ISO compared to that of SD. Venous lactate output and cardiac LDH activity were augmented in SHR as influenced by ISO. These results demonstrate that coronary reactive and functional hyperemia was dpressed in SHR, which cold be explained by alterations in the cytosolic phosphorylation potential and the cytosolic redox state manipulated by LDH, and by abnormal free calcium handling.

• 대한본초학회지
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• 제27권2호
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• pp.77-83
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• 2012

Objectives : This work was designed to investigate the effect of The root of Achyranthes japonica Nakai (AJN) water extract on serum deprivation reperfusion-induced apoptosis in PC-12 cells and transient middle cerebral artery occlusion (tMCAO)-induced ischemic brains of rats. Methods : Apoptosis in PC12 cells was induced by serum deprivation and reperfusion. The cells were treated with AJN water extract at doses of 0.5 and 1.0 mg/ml for 24 hr after inducing the apoptosis. Cell viability was determined by WST-1 assay. The expression of caspase-3 protein was determined by Western blot. Ischemic brains were prepared from tMCAO-induced ischemic rats after oral administration with AJN at dose of 50 and 100 mg/kg, and then brain infarction was measured by TTC staining. Results : AJN significantly increased the cell viability in apoptocic-induced PC-12 cells, and also decreased the expression of caspase-3 protein. Furthermore, the administration of AJN significantly inhibited tMCAO-induced brain infarction in rats. Conclusions : Our results suggest that AJN extract has a neuroprotective property via suppressing the apoptosis in PC12 cells and the infarction of ischemic brains.

• Molecules and Cells
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• 제40권12호
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• pp.916-924
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• 2017

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that $Gadd45{\beta}$ (growth arrest DNA damage-inducible gene $45{\beta}$) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of $Gadd45{\beta}$. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting $Gadd45{\beta}$.

• 동의생리병리학회지
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• 제17권5호
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• pp.1194-1201
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centries as a therapeutic agent of vertigo caused by deficiency of qi(氣) and blood(血). Effect of Aurantii Fructus(AF) take off the phlegm by promoting the circulation of qi, Gastrodae Rhizoma(GR) has effects treating for headarch, vertigo by calming the liver and suppressing hyperactivity of the liver-yang (陽). I investigated whether injection of JGT adding AFㆍGR extract(JTG) affects cerebral hemodynamics [regional cerebral blood f1ow(rCBF), pial arterial diameter(PAD) in cerebral ischemia rats by MCA occlusion method, and I designed to make manifest whether JTG is mediated by adrenergic β-receptor, cyclooxygenase or guanylate cyclase. The changes of rCBF was determinated by laser-doppler flowmetry(LDF), and the changes of PAD was determinated by video microscope and width analyzer. The results were as follows in cerebral ischemic rats; The changes of rCBF and PAD were increased stabilizly by treatment with JTG(10 ㎎/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with propranolol and indomethacin were increased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. Pretreatment methylene blue was decreased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. In conclusion, JTG causes a diverse response of rCBF and PAD, and action of JTG is mediated by adrenergic β-receptor and cyclooxygenase. I suggest that JTG has an anti-ischemic effect through the improvement of crebral hemodynamics.

• 대한한의학회지
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• 제23권4호
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• pp.113-124
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• 2002

Objects: This research was conducted to investigate the protective effect of Bupleuri Radix against ischemic damage using PC12 cells and global ischemia in gerbils, Methods: To observe the protective effect of Bupleuri Radixon ischemic damage, viability and changes in activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and production of malondialdehyde (MDA) were observed after treating PC12 cells with Bupleuri Radix during ischemic damage. Gerbils were divided into three groups: a normal group, a 5-minute two-vessel occlusion (2VO) group and a Bupleun Radix administered group after 2VO. The CCAs were occluded by microclip for 5 minutes, Bupleuri Radix was administered orally for 7 days after 2VO. Histological analysis was performed on the 7th day. For histological analysis, the brain tissue was stained with 1 % of cresyl violet solution. Results: 1. Bupleuri Radix has a protective effect against ischemia in the CA1 area of the gerbil's hippocampus 7 days after 5-minute occlusion. 2. In the hypoxia/reperfusion model using PC12 cells, the Bupleuri Radix has a protective effect against ischemia in the dose of 0.2{\;}\mu\textrm{g}/ml,2{\;}\mu\textrm{g}/ml{\;}and{\;} 20{\;}\mu\textrm{g}/ml$. 3. Bupleuri Radix increased the activities of glutathione peroxidase and catalase. 4. The increased activity of superoxidedismutase (SOD) by ischemic damage might have been induced as an act of self-protection. This study suggests that Bupleuri Radix has some neuroprotective effect against neuronal damage following cerebral ischemia in vivo with a widely used experimental model of cerebral ischemia in Mongolian gerbils. Bupleuri Radix also has protective effect on a hypoxia/reperfusion cell culture model using PC12 cells. Conclusions: Bupleuri Radix has protective effect against ischemic brain damage during the early stages of ischemia.

• Journal of Korean Neurosurgical Society
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• 제59권4호
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• pp.379-384
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• 2016

Objective : Mechanical thrombectomy (MT) for acute intracranial internal carotid artery (ICA) occlusion is often complicated by difficult revascularization and non-involved territory embolization possibly related with larger clot-burden. This study aims to evaluate the efficacy of proximal aspiration thrombectomy (PAT) using a balloon-tipped guide catheter for clot-burden reduction in such cases with period-to-period analysis (period 1 : standard MT without PAT; period 2 : PAT first, then standard MT for the remaining occlusion). Methods : Eighty-six patients who underwent MT for acute intracranial ICA occlusion were included in this analysis from the prospectively maintained stroke registry (33 patients in period 1 and 53 in period 2). In period 2, 'responder' was defined as a case where some amount of clot was retrieved by PAT and the following angiography showed partial or full recanalization. Results : Fifteen of fifty-three patients in period 2 (28.3%) were 'responders' to PAT. There was a significantly higher incidence of atrial fibrillation in the 'responder' subgroup. Period 2 showed a significantly shorter puncture-to-reperfusion time (94.5 minutes vs. 56.0 minutes; p=0.002), a significantly higher Thrombolysis in Cerebral Infarction of 2b-3 reperfusion (45.5% vs. 73.6%; p=0.009), but only a trend for better 3-month favorable outcome (mRS 0-2; 36.4% vs. 54.7%; p=0.097). There was no increase in the incidence of procedure-related complications or intracranial hemorrhage in period 2. Conclusion : A strategy of PAT before standard MT may result in shorter puncture-to-reperfusion time and better angiographic outcome than a strategy of standard MT for acute intracranial ICA occlusion.

• Toxicological Research
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• 제13권4호
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• pp.359-365
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• 1997

Many factors are known to be responsible for cerebral ischemic injury, such as excitatory neurotransmitters, increased intraneuronal calcium, or disturbance of cellular energy metabolism. Recently, oxygen free radicals, formed during ischemia/reperfusion, have been proposed as one of the main causes of ischemia/reperfusion injury. Therefore, to investigate the role of oxygen free radical during ischemia/reperfusion, in the present study the effect of endogenous oxygen free radical scavenger, superoxide dismutase / catalase(SOD / catalase) on the release of [$^3$H]-5-hydroxytryptamine([$^3$H]-5-HT) during hypoxia/reoxygenation in rat hippocampal slices was measured. The hippocampus was obtained from the rat brain and sliced 400 gm thickness with manual chopper. After 30 min's preincubation in the normal buffer, the slices were incubated for 20 min in a buffer containing [$^3$H]-5-HT(0.1 $\mu$M, 74 $\mu$Ci) for uptake, and washed. To measure the release of [$^3$H]-5-HT into the buffer, the incubation medium was drained off and refilled every ten minutes through a sequence of 14 tubes. Induction of hypoxia for 20 min (gassing it with 95% N$_2$/5% CO$_2$) was done in the 6th and 7th tube, and oxygen free radical scavenger, SOD / catalase was added 10 minutes prior to induction of hypoxia. The radioactivity in each buffer and the tissue were counted using liquid scintillation counter and the results were expressed as a percentage of the total activity. When slices were exposed to hypoxia for 20 min, [$^3$H]-5-HT release was markedly decreased and a rebound release of [$^3$H]-5-HT was observed on the post-hypoxic reoxygenation period. SOD / catalase did not changed the release of [$^3$H]-5-HT in control group, but inhibited the decrease of [$^3$H]-5-HT release in hypoxic period and rebound increase of [$^3$H]-5-HT in reoxygenation period. This result suggest that superoxide anion may play a role in the hypoxic-, and reoxygenation-induced change of [$^3$H]-5-HT release in rat hippocampal slices.