• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.185-191
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• 2011

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.265-273
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• 2016

BACKGROUND/OBJECTIVES: The inhibitory effect of Hijikia fusiforme (HF) extracts on degenerative osteoarthritis was examined in primary cultured rat cartilage cells and a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. MATERIALS/METHODS: In vitro, cell survival and the expression of matrix metalloproteinases (MMPs), collagen type I, collagen type II, aggrecan, and tissue inhibitor of metalloproteinases (TIMPs) was measured after $H_2O_2$ ($800{\mu}M$, 2 hr) treatment in primary chondrocytes. In vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats, and then RH500, HFE250 and HFE500 were administered orally once a day for 28 days. To determine the anti-inflammatory effects of HFE, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) expression were measured. In addition, real-time PCR was performed to measure the genetic expression of MMPs, collagen type I, collagen type II, aggrecan, and TIMPs. RESULTS: In the in vitro assay, cell survival after $H_2O_2$ treatment was increased by HFE extract (20% EtOH). In addition, anabolic factors (genetic expression of collagen type I, II, and aggrecan) were increased by HFE extract (20% EtOH). However, the genetic expression of MMP-3 and 7, known as catabolic factors were significantly inhibited by treatment with HFE extract (20% EtOH). In the in vivo assay, anabolic factors (genetic expression of collagen type I, II, aggrecan, and TIMPs) were increased by oral administration of HFE extract. However, the genetic expression of MMP-3 and 7, known as catabolic factors, and production of NO and $PGE_2$ were significantly inhibited by treatment with oral administration of HFE extract. CONCLUSION: HFE extract inhibited articular cartilage degeneration through preventing extracellular matrix degradation and chondrocyte injury.

• 한국신재생에너지학회:학술대회논문집
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• 2008.10a
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• pp.188-191
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• 2008

There have been many methods for producing natural gas from gas hydrate reservoirs in permafrost and sea floor sediments. It is well knownthat the depressurization should be a best option for Class 1 gas hydrate deposit, which is composed of tow layers: hydrate bearing layer and an underlying free gas. However many of gas hydrate reservoirs in sea floor sediments are classified as Class 2 that is composed of gas hydrate layer and mobile water, and Class 3 that is a single gas hydrate layer. The most appropriate production methods among the present methods such as thermal stimulation, inhibitor injection, and controlled oxidation are still under development with considering the gas hydrate reservoir characteristics. In East Sea of Korea, it is presumed that the thick fractured shale deposits could be Class 2 or 3, which is similar to the gas hydrate discovered offshore India. Therefore it is needed to evaluate the possible production methods for economic production of natural gas from gas hydrate reservoir. Here we would like to present the production of natural gas from gas hydrate deposit in East Sea with industrial flue gases from steel company, refineries, and other sources. The existing industrial complex in Gyeongbuk province is not far from gas hydrate reservoir of East Sea, thus the carbon dioxide in flue gas could be used to replace methane in gas hydrate. This approach is attractive due to the suggestion of natural gas productionby use of industrial flue gas, which contribute to the reduction of carbon dioxide emission in industrial complex. As a feasibility study, we did the NMR experiments to study the replacement reaction of carbon dioxide with methane in gas hydrate cages. The in-situ NMR measurement suggeststhat 42% of methane in hydrate cages have been replaced by carbon dioxide and nitrogen in preliminary test. Further studies are presented to evaluate the replacement ratio of methane hydrate at corresponding flue gas concentration.

• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.357-366
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• 2004

We studied the effect of propofol (PPF) on the endothelium-dependent vascular responses in isolated rat thoracic aorta. In aortic rings with endothelium, PPF inhibited the phenylephrine (PE)-induced contraction in a concentration-dependent manner. In PE-precontracted preparations, PPF attenuated the endothelium-dependent relaxation by acetylcholine but not by A23187. And PPF did not attenuate the endothelium-independent relaxation by sodium nitroprusside (SNP). The relaxation induced by acetylcholine in PE-precontracted aortic rings was significantly augmented by zaprinast, a cGMP-specific phosphodiesterase inhibitor, and this augmentation was inhibited by PPF. Although SNP-induced relaxation was significantly augmented by zaprinast, this augmentation was not inhibited by PPF. In preparations preconstricted with PE, the PPF-induced relaxation was inhibited by atropine. In addition, PPF attenuated the vasorelaxation by phosphodiesterase inhibitors (IBMX, Ro20-1724 or zaprinast except milrinone). In vivo, the infusion of acetylcholine and SNP showed decreased arterial blood pressure in rats. The pre-injection of PPF inhibited the acetylcholine-induced blood pressure lowering, but not the SNP-induced blood pressure lowering. These results suggest that PPF can attenuate in part the acetylcholine-induced vasorelaxation and blood pressure lowering through the inhibition of the acetylcholine receptor-mediated endothelium-derived relaxing factor by acting on endothelium. It is considered that the inhibitory effect of PPF on the vasorelaxation is due to the decreased level of cGMP which can be attributed to the inhibition of the muscarinic receptor and/or receptor-G-protein interaction.

• Journal of Periodontal and Implant Science
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• v.31 no.2
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• pp.389-400
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• 2001

Previous studies have demonstrated an increase in bone mass and density with the use of bisphosphonate in osteoporosis. This agent acts as an inhibitor of osteoclastic activity, and results in increase of net osteoblastic activity. Currently, it has been reported that bisphosphonate has direct effect on osteoblast. This study was designed to evaluate the effect of alendronate on bone regeneration in defect of rat calvaria. The animals used for these experiments were 48 male rats, over 6-8 weeks old. They were divided into three groups according to the dose of alendronate($MK-217^{(R)}$, Merck, USA) administered. After the calvarial defects were surgically created, the rats received a peritoneal alendronate(0.25mg/kg) in group I, a peritoneal alendronate(1.25mg/kg) in group II, and a peritoneal normal saline injection in the control group. Three and six weeks later, blood was sampled and evaluated for alkaline phosphatase activity. The animals were sacrificed for histological observation and histometric analysis of the level of bone formation. The alkaline phosphatase activity was similar in three groups at 3 weeks of experiment. The activity at 6 weeks increased more than twice, compared to 3 weeks, and was slightly higher in group I than the other two groups. In histological observation, all the groups at 3 weeks, osteoblast rimming and new bone formation were observed along the defect margin. At 6 weeks, the defect was almost closed with new and more mature bone, but new bone is thinner than original bone in the central portion of defect. In histometric analysis, group I and II at 3 weeks showed significantly greater new bone formation than the control, and all the groups at 6 weeks showed similar amount of bone formation. These result suggest that alendronate administration in the dose of 0.25mg/kg and 1.25mg/kg promote osseous regeneration.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.106-110
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• 2007

Background: A phosphodiesterase 5 inhibitor, sildenafil, has been effective against nociception. Several lines of evidence have demonstrated the role of the GABAergic pathway in the modulation of nociception. The impact of the GABA receptors on sildenafil was studied using the formalin test at the spinal level. Methods: Male SD rats were prepared for intrathecal catheterization. The formalin test was induced by subcutaneous injection of formalin solution. The change in the activity of sildenafil was examined after pre-treatment with GABA receptor antagonists ($GABA_A$ receptor antagonist, bicuculline; $GABA_B$ receptor antagonist, saclofen). Results: Intrathecal sildenafil dose-dependently attenuated the flinching observed during phase 1 and 2 in the formalin test. The antinociceptive effect of sildenafil was reversed by the $GABA_B$ receptor antagonist (saclofen) but not by the $GABA_A$ receptor antagonist (bicuculline) in both phases. Conclusions: Intrathecal sildenafil suppressed acute pain and the facilitated pain state. The antinociception of sildenafil is mediated via the $GABA_B$ receptor, but not the $GABA_A$ receptor, at the spinal level.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.345-351
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• 1998

The role of nitric oxide (NO) in the hemorrhagic hypotension was examined using a NO synthase inhibitor, $N^{\omega}-nitro-L-arginine$ methyl ester (L-NAME), in conscious rats. The rats were bled at a constant rate (2 ml/kg/min) through a femoral arterial catheter until the mean arterial pressure (MAP) was reduced by 50 mmHg. We studied the responses to hemorrhage under normal condition (Control) and after the pretreatment with 3 doses of L-NAME (1.6, 8, 40 mg/kg i.v. of NOX1.6, NOX8, and NOX40, respectively). Intravenous bolus injection of L-NAME produced a sustained increase in MAP and decrease in heart rate (HR). During hemorrhage, the MAP fell faster in the NOX8 and NOX40-treated groups than in Control group, but the control group showed same response to NOX1.6. HR greatly increased in NOX groups. The recovery from hemorrhagic hypotension was slowed in the control group, which was not treated with L-NAME. In comparison with the control group, NOX8 and NOX1.6-treated groups registered a significant recovery in MAP during the 15 min recovery period, but NOX40 brought about only a slight increase in MAP. NO precursor, L-arginine (150 mg/kg i.v.), produced significant bradycardic responses before and after hemorrhage and significant depressor response only after hemorrhagic hypotension regardless of pretreatment with L-NAME. These data suggest that the role of NO in blood pressure regulation is greater after hemorrhagic hypotension than basal condition, but the effect of NO can be detrimental to the recovery from hemorrhagic hypotension. In addition, the bradycardic response of L-arginine provides indirect evidence that NO may inhibit sympathetic activity, especially after hemorrhagic hypotension.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.21-28
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• 2006

Gadolinium chloride ($GdCl_{3}$) was known to block Kupffer cells and generally its toxicity study based on blocking these cells. Therefore, $GdCl_{3}$ frequently used to study toxic mechanisms of hepatotoxicants inducing injury through Kupffer cells. We also tried to investigate the effect of $GdCl_{3}\;on\;CCl_{4}$ toxicity, typical hepatotoxicants. Administration of $GdCl_{3}$ to mice significantly suppressed AST (asparatate amino transferase), ALT (alanine amino transferase) levels which were increased by $CCl_{4}$ treatment. However, $GdCl_{3}$ didn't inhibit the phagocytotic activity of Kupffer cells. Malondialdehyde (MDA) is a good indicator of the degree of lipid peroxidation. In this study, MDA increased by $GdCl_{3}$ administration not by $CCl_{4}$. To understand the toxicity of $GdCl_{3}$, we analyzed global gene expression profile of mice liver after acute $GdCl_{3}$ injection. Four hundred fifty two genes were differentially expressed with more than 2-fold in at least one time point among 3 hr, 6 hr, and 24 hr. Several genes involved in fibrogenesis regulation. Several types of pro-collagens (Col1a2, Col5a2, Col6a3, and Col13a1) and tissue inhibitor of metal-loproteinase1 (TIMP1) were up regulated during all the time points. Genes related to growth factors, chemokines, and oxidative stress, which were known to control fibrogenesis, were significantly changed. In addition, $GdCl_{3}$ induced abnormal regulation between lipid synthesis and degradation related genes. These data will provide the information about influence of $GdCl_{3}$ to hepatotoxicity.

• Development and Reproduction
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• v.24 no.4
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• pp.297-306
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• 2020

Repetitive changes in the intracellular calcium concentration ([Ca²⁺]i) triggers egg activation, including cortical granule exocytosis, resumption of second meiosis, block to polyspermy, and initiating embryonic development. [Ca²⁺]i oscillations that continue for several hours, are required for the early events of egg activation and possibly connected to further development to the blastocyst stage. The sources of Ca²⁺ ion elevation during [Ca²⁺]i oscillations are Ca²⁺ release from endoplasmic reticulum through inositol 1,4,5 tri-phosphate receptor and Ca²⁺ ion influx through Ca²⁺ channel on the plasma membrane. Ca²⁺ channels have been characterized into voltage-dependent Ca²⁺ channels (VDCCs), ligand-gated Ca²⁺ channel, and leak-channel. VDCCs expressed on muscle cell or neuron is specified into L, T, N, P, Q, and R type VDCs by their activation threshold or their sensitivity to peptide toxins isolated from cone snails and spiders. The present study was aimed to investigate the localization pattern of N and P/Q type voltage-dependent calcium channels in mouse eggs and the role in fertilization. [Ca²⁺]i oscillation was observed in a Ca²⁺ contained medium with sperm factor or adenophostin A injection but disappeared in Ca²⁺ free medium. Ca²⁺ influx was decreased by Lat A. N-VDCC specific inhibitor, ω-Conotoxin CVIIA induced abnormal [Ca²⁺]i oscillation profiles in SrCl₂ treatment. N or P/Q type VDC were distributed on the plasma membrane in cortical cluster form, not in the cytoplasm. Ca²⁺ influx is essential for [Ca²⁺]i oscillation during mammalian fertilization. This Ca²⁺ influx might be controlled through the N or P/Q type VDCCs. Abnormal VDCCs expression of eggs could be tested in fertilization failure or low fertilization eggs in subfertility women.

• Molecules and Cells
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• v.42 no.3
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• pp.218-227
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• 2019

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.