• Title/Summary/Keyword: Cell Injuries

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The Effects of Kami-bangpungtongseong-san Extracts on the Mouse Liver and Kidney Toxicated by Mercuric Chloride Subcutaneous Injection (가미방풍통성산(加味防風通聖散)이 수은의 피하 주입으로 중독된 마우스의 간 및 신기능에 미치는 영향)

  • Yang, Joon-Hyoung;Hong, Seong-Ug
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.1-12
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    • 2010
  • Objective : For this study, mice on mercurial toxication were given mercuric subcutaneous injection to their abdomen factitiously. After delivering Kami- bangpungtongseong-san(KBT) extracts to the mice by oral administration, we observed changes from liver and kidney of mice. Method : The BALB/c mice were distributed into three groups: No treated group(Normal group), Mercuric chloride subcutaneous injection group(Control group), Kami-bangpungtongseong-san-treated group (Sample group). KBT Extracts were delivered orally in 7 days. We observed involution of liver, necrosis of liver and cell plate loss of liver, lipid peroxidation CYP1A1 expression. We observed involution of proximal convoluted tubules, hypertrophy of Bowman's capsule, periodic acid-Schiff(PAS)'s positive reaction of proximal convoluted tubules, heat shock protein(HSP)700's positive reaction in glomerulus. For the charting the results, image analysis was taken. The result of image analysis was verified significance by Sigmaplot 2000(P<0.05). Result : The mice' liver on mercurial toxication were relieved involution of liver, necrosis of liver, and cell plate loss of liver and also declined lipid peroxidation and CYP1A1 expression. The mice' kidney on mercurial toxication were relieved involution of proximal convoluted tubules, hypertrophy of Bowman's capsule and increasing PAS's positive reaction of proximal convoluted tubules. On the other hand it was declined HSP700's positive reaction in glomerulus. Conclusion : According to the result of study, we think that we can expect to the effect of KBT extracts' therapeutic action to tissue injuries of the mice' liver and kidney on acute mercurial toxication.

Neuroprotective effect of the water extract of Angelicae Gigantis Radix Palva in ischemic stroke rats (허혈성 뇌졸중 흰쥐에서 당귀미 열수추출물의 혈관신생인자 발현 조절을 통한 신경세포 보호작용에 대한 연구)

  • Park, Ki-Ho;Oh, Tae-Woo;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.27 no.2
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    • pp.61-67
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    • 2012
  • Objective : Angelica Gigas Nakai is a popular oriental medicine used for the treatment of vascular diseases. The aim of this study is to investigate neuroprotective effect of the water extract of Anelicae Gigantis Radix Palva (AG) in transient middle cerebral artery occlusion (tMCAO)-induced ischemic rats via the regulation of angiogenesis-related molecules. Methods : Sprague-Dawley rats were intraperitoneally administrated with AG water extract at doses of 10, 25, 50 mg/kg body weight after tMCAO (90 min occlusion). reperfusion for 24 hr infarction volumes were measured by 2,3,5-tetrazolium chloride (TTC) staining. Brain tissues were observed neuronal cell injuries by nissl staining, and also brain-blood barrier (BBB) permeability change by evans blue. Expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Tie-2 receptor protein in brain tissues was determined by western blot. Results : AG water extract significantly reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability and expression of VEGF protein dose-dependently. Ang-1 protein was increased dose-dependantly, not significantly. Conclusion : This study suggests that AG water extract shows neuroprotective effect by preventing BBB breakdown, with regulating angiogenesis factor VEGF and Ang-1.

Pharmacology of enantiomers of higenamine and related tetrahydroisoquinolines

  • Park, Min-Kyu;Huh, Ja-Myung;Lee, Young-Soo;Kang, Young-Jin;Seo, Han-Geuk;Lee, Jae-Heun;Park, Hye-Sook-Yun-;Lee, Duck-Hyung;Chang, Ki-Churl
    • 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.

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Protective Effect of Allomyrina dichotoma Larva Extract on tert-butyl Hydroperoxide-induced Oxidative Hepatotoxicity

  • Lee, Kyung-Jin;Lee, Jong-Bin
    • Korean Journal of Environmental Biology
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    • v.27 no.2
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    • pp.230-236
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    • 2009
  • An extract of Allomyrina dichotoma larva (ADL), one of the insects used most frequently in traditional Chinese medicine for the treatment of liver diseases such as hepatocirrhosis and hepatofibrosis, was assessed for antioxidant bioactivity in this study. In the current work, we have investigated the protective effects of ADL extracts on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in cultured hepa1c1c7 cells and in the mouse liver. The treatment of the hepa1c1c7 cells with ADL extracts induced a significant reduction of t-BHP-induced oxidative injuries, as determined by cell cytotoxicity, lipid peroxidation (LPO) and reactive oxygen species contents, in a dose-dependent manner. Moreover, ADL extracts evidenced a protective effect against t-BHPinduced oxidative DNA damage, as revealed by the results of the Comet assay in hepa1c1c7 cells. ADL extracts also protected against hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and $H_2O_2$. In addition, ADL extracts were shown to be able to quench 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. Our in vivo study revealed that ADL extracts pretreatment applied prior to t-BHP administration significantly prevented an increase in the serum levels of hepatic enzyme markers and reduced LPO in the mouse liver in a dose-dependent manner. Taken together, these results suggest that the protective effects of ADL extracts against t-BHP-induced hepatotoxicity may be attributable, at least in part, to its ability to scavenge free oxygen radicals, and to protect against DNA damage due to oxidative stress.

Antioxidant Effect and Liver Protection Effect of Spatholobi Caulis Water Extract (계혈등 물추출물의 항산화 및 간보호효과)

  • Lee, Jae-Jun;Choi, Hong-Sik;Kim, Seung-Mo
    • The Korea Journal of Herbology
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    • v.26 no.3
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    • pp.47-56
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    • 2011
  • Objectives : This study investigated whether the water extract of Spatholobi Caulis (SCE) has the ability to protect hepatocyte against oxidative stress induced by tert-butylhydroperoxide (tBHP) in vitro and $CCl_4$ in vivo. Methods : In vitro, HepG2 cells pre-treated with Spatholobi Caulis water extract (1, 3, 10, $30{\mu}g$/ml) for 12h and further incubated with tBHP ($100{\mu}M$) for the next 12h. Cell viability was assessed by MTT assay. In vivo, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, injected with $CCl_4$ 1 mg/kg body weight to induce acute liver damage. Results : Treatment with SCE inhibited cell death induced by tBHP, as evidenced by alterations in the levels of the proteins associated with apoptosis:SCE prevented a decrease in $Bcl_2$, and cleavage of poly(ADP-ribose)polymerase and pro-caspase-3. Moreover, SCE inhibited the ability of tBHP to generate $H_2O_2$ production, thereby restoring GSH content. Moreover, SCE treatments in rats effectively decreased liver injuries induced by a single dose of $CCl_4$, as evidenced by decreases in hepatic degeneration and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. Consistently, treatments of SCE also protected liver in rats stimulated by $CCl_4$, as indicated by restoration GSH and prevention of MDA in the liver. Conclusions : SCE has the ability 1) to protect hepatocyte against oxidative stress induced by tBHP and 2) to prevent $CCl_4$-inducible acute liver toxicity. Present findings may be informative not only in elucidating the pharmacological mechanism of Spatholobi Caulis, but in determining its potential application for oxidative cellular damage in the liver.

The Protective Effects of Seokchangpowonji-san on $H_2O_2$-Mediated Cell Death of Neuro 2A as an Alzheimer Model System (산화적 손상에 의한 Neuro 2A 치매모델에서 석창포원지산의 방어효과)

  • Yim Jun-Mo;Lee Min-Goo;Yun Jong-Min;Lee In;Moon Byung-Soon
    • The Journal of Korean Medicine
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    • v.26 no.1 s.61
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    • pp.161-173
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    • 2005
  • Objective : The water extract of Seokchangpowonji-san (SWS) has traditionally been used for treatment of dementia in oriental medicine. However, little is known about the mechanism by which the water extract of SWS rescues cells from neurodegenerative disease such as Alzheimer's disease. Methods & Results: This study was designed to investigate the protective mechanisms of SWS on $\beta-amyloid$ or $H_2O_2$-induced$ cytotoxicity in neuro 2A cells. $H_2O_2$ markedly decreased the viability of neuro 2A cells, which was characterized by apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the water extract of SWS significantly reduced $H_2O_2-induced$ cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Also, the. extract prevented the mitochondrial dysfunction including the disruption of mitochondria membrane permeability transition (MPT) and the modulation in expression of Bcl-2 family proteins in $H_2O_2­treated$ neuro 2A cells. Furthermore, pretreatment with SWS inhibited the activation of caspase-3, and in turn, degradation of ICAD/DFF45 was completely abolished in $H_2O_2-treated$ cells. Conclusion: Taken together, the data suggest that the protective effects of the water extract of SWS against $\beta-amyloid$ induced oxidative injuries may be achieved through modulation of mitochondrial dysfunction.

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Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

  • Kim, Yonghoon;Kim, Jeongtae;Ahn, Meejung;Shin, Taekyun
    • Anatomy and Cell Biology
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    • v.50 no.3
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    • pp.207-213
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    • 2017
  • Glycogen synthase kinase $(GSK)-3{\beta}$ and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of $GSK-3{\beta}$, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative $GSK-3{\beta}$-associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of $GSK-3{\beta}$ (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that $GSK-3{\beta}$ becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of $GSK-3{\beta}$ and the associated molecules Nrf-2 and HO-1.

Identification of novel potential drugs and miRNAs biomarkers in lung cancer based on gene co-expression network analysis

  • Sara Hajipour;Sayed Mostafa Hosseini;Shiva Irani;Mahmood Tavallaie
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.38.1-38.8
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    • 2023
  • Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DEmiRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co- expression network. Next, four modules were selected based on the Zsummary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.

Study on Effect of Moxibustion in Myofiber Regeneration and Muscle fatigability (뜸이 근섬유 조직재생 및 피로회복에 미치는 영향에 대한 문헌적 고찰)

  • Ko, Min-Kyung;Lee, Jeong-Hwan;Hong, Kwon-Eui
    • Journal of Acupuncture Research
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    • v.28 no.6
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    • pp.19-26
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    • 2011
  • Objectives : Although moxibustion is one of the most frequently used methods in oriental medicine, effect of moxibustion in myofiber regeneration and muscle fatigability is hardly studied. This study was researched to observe the effect of moxibustion in myofiber regeneration and muscle fatigability. Methods : We reviewed studies which contained moxibustion and published after 2000s in Pubmed. We also reviewed domestic studies in RISS, KISS and DBPIA, but only three studies were researched. Results : In myofiber regeneration, moxibuston has improved blood flow in muscle tissue and recover tissue injuries fast. Especially, moxibustion trigger an increse of HSP levels, which protect the cell against irreversible damage, apoptosis and death. Thus, that helps to stimulate myofiber regeneration. In many studies, as moxibustion stimulate PMRs and decrease fatigue substances, such as lactate acid and creatinine, so moxibustion is considered to be effective to recover and prevent muscle fatigability. Based on such effects, moxibustion is considered to have an effect on TPs, but have been hardly studied. Conclusions : Although Moxibution is considered to be effective in myofiber regeneration and muscle fatigability, futher study is needed.

A 10-year-old Boy with Microscopic Hematuria and Renal Biopsy Findings Mimicking Fabry Disease

  • Chung, Woo Yeong;Kang, Mi Seon
    • Childhood Kidney Diseases
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    • v.20 no.2
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    • pp.79-82
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    • 2016
  • Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme ${\alpha}-galactosidase$ A, resulting in the accumulation of glycosphingolipids within the lysosomes of various cell types. It has a wide spectrum of clinical phenotypes, and renal failure is a serious complication. Fabry disease is confirmed either by measurement of ${\alpha}-galactosidase$ A activity or by genetic testing for GLA mutations. Renal biopsy findings on light microscopy, specifically enlarged podocytes with foamy cytoplasm, and osmiophilic inclusion bodies in the cytoplasm in all types of renal cells on electron microscopy, are characteristic of this disease. The predominant differential diagnosis is iatrogenic phospholipidosis in association with certain drugs that can cause cellular injuries indistinguishable from Fabry disease. Here, we report the case of a 10-year-old boy with microscopic hematuria who underwent a renal biopsy that showed morphological findings consistent with Fabry disease, although the patient had neither a GLA mutation nor a history of drug consumption. Six years later, spontaneous regression of this renal pathology was observed in a second renal biopsy examination.