• Title/Summary/Keyword: induced neurotoxicity

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Treatment Strategies for Primary Central Nervous System Lymphoma (원발성 중추신경계 림프종의 치료전략)

  • Kim, Il-Man;Lee, Chang Young;Son, Eun Ik;Kim, Dong Won;Yim, Man Bin;Kim, Sang Pyo
    • Journal of Korean Neurosurgical Society
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    • v.30 no.3
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    • pp.334-341
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    • 2001
  • Objective : We have currently changed treatment strategies to methotrexate(MTX)-based preirradiation chemotherapy with subsequent planned radiation for the initial therapy of primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the results of treating PCNSL with chemotherapy plus radiotherapy (CRT) or radiotherapy(RT) alone. Method and Material : This study involved 10 females and 3 males patients with a mean age of 54.2 years. All patients underwent surgery, open(8 cases) or stereotactic biopsy(5 cases) for histological diagnosis. Eleven tumors were diffuse large B-cell lymphomas. Tumor volume change in the follow-up images and survival time were evaluated in patients treated with CRT and RT alone. In the beginning, two patients received ProMACE-Cytabom chemotherapeutic regimen, but did not complete the course and died of progressive tumor 8 and 9 months after diagnosis, respectively. One patient died at 6 months before chemotherapy. These three were excluded from the survival analysis. Five patients(RT group) completed full courses of cranial irradiation with or without boost. For the current combined modality treatment, high-dose MTXbased chemotherapy(systemic and intrathecal MTX, IV vincristine, and oral procarbazine) followed by whole brain irrdiation to 45Gy to tumor was introduced in 5 patients of CRT group. Result : A complete response was achieved in three of five who received RT only and in all of five who received CRT. All patients in CRT groups are in disease free status at a mean 23 months following therapy. The RT group patients refused any additional salvage therapy at tumor relapse and survived at mean 20 months from diagnosis. The Karnofsky performance status improved in eight of ten patients with treatment. The treatment toxicity included leukoencephalopathy in RT group and severe leukopenia, transient hepatitis, avascular necrosis of femoral head, hearing loss, and amenorrhea in CRT group, respectively. Conclusion : The combined modality therapy of MTX-based chemotherapy plus radiotherapy for PCNSL may enhance tumor response and improve patient survival. The patients who received CRT should be carefully followed up because of the higher risk of treatment-induced late neurotoxicity.

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Biological Activities of Poria cocos Wolf and Corni fructus Extracts based on their extraction solvent (추출용매에 따른 복령(Poria cocos Wolf)과 산수유(Corni fructus) 추출물의 생리활성 효과 비교)

  • Oh, Hee-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.36 no.4
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    • pp.1303-1311
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    • 2019
  • This study was to investigate the antioxidant, anti-inflammatory and neuronal cell protective effects of Poria cocos Wolf and Corni fructus extracted by water and 70% ethanol. Total polyphenol content in water extract of Poria cocos Wolf was significantly higher than those of other extracts. DPPH and ABTS free radical scavenging activity in water extract of Corni fructus was higher than those of other extracts. DPPH and ABTS free radical scavenging activity were increased in a dose-dependent manners. In order to effectively extract total polyphenol contents and anti-oxidant components in Poria cocos Wolf and Corni fructus, hot water extraction method is more efficient than ethanol extraction method. Poria cocos extracts were found to be a superior NO production inhibitory effect compared to Corni fructus extracts. In a neuronal cell viability assay using MPP+, the water extract of Poria cocos Wolf protected against MPP+-induced neurotoxicity than those of Corni fructus extract. It is considered to be a potential functional material with antioxidant, anti-inflammatory and neuronal protective effect against to oxidative stress according to the extract methods of extracting Poria cocos Wolf and Corni fructus.

Antioxidant and Neuroprotective Effects of Gamisoyo-san (가미소요산(加味逍遙散)의 항산화효과(抗酸化效果)및 신경세포(神經細胞) 보호효과(保護效果))

  • Lee, Seung-Han;Lee, Jin-Moo;Cho, Jung-Hoon;Lee, Chang-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.23 no.3
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    • pp.1-13
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    • 2010
  • Purpose: These studies were undertaken to evaluate the anti-oxidative and neuroprotective effects of Gamisoyo-san(GMSYS). Materials and Methods: We studied the antioxidant effects of GMSYS by assessing the DPPH free radical and the ABTS radical cation inhibition activities, the total polyphenolic contents(TPC). To evaluate the effects of GMSYS in the human neuroblastoma cells, we measured the cell viabilities in SH-SY5Y cells treated with GMSYS. Then we observed the protective effects of GMSYS against 6-OHDA induced neurotoxicity in SH-SY5Y cells. To confirm the neuroprotective effects of GMSYS in the primary culture of mesencephalic dopaminergic cells, we counted the TH-immunopositive cells and measured the NO and TNF-$\alpha$ after the treatment of GMSYS and 6-OHDA. Results: The DPPH free radical and the ABTS radical cation inhibition activities were increased in a dose dependent manner and the IC50 were $133.60{\mu}g/m{\ell}$ and $106.20{\mu}g/m{\ell}$, respectively. The TPC was 0.78%. There were no differences between the various concentrations of GMSYS and the control in the cell viability of SH-SY5Y cells. The neuroprotective effects of GMSYS were shown in the co-treatment group at the low concentrations of $25{\mu}g/m{\ell}$ and the post-treatment group at all concentrations. After the treatment of GMSYS and 6-OHDA in the primary culture of dopaminergic cells, the TH-immunopositive cells were significantly increased in $0.2{\mu}g/m{\ell}$ of GMSYS than the 6-OHDA group. The NO and TNF-$\alpha$ were significantly decreased in $0.2{\mu}g/m{\ell}$ of GMSYS than the 6-OHDA group. Conclusions: This study shows that GMSYS has the antioxidant and neuroprotective effects, especially in the mesencephalic dopaminergic cells. We suggest that GMSYS could be useful for the treatment of postmenopausal depression related with the degeneration of dopamine neuron.

Dieckol Attenuates Microglia-mediated Neuronal Cell Death via ERK, Akt and NADPH Oxidase-mediated Pathways

  • Cui, Yanji;Park, Jee-Yun;Wu, Jinji;Lee, Ji Hyung;Yang, Yoon-Sil;Kang, Moon-Seok;Jung, Sung-Cherl;Park, Joo Min;Yoo, Eun-Sook;Kim, Seong-Ho;Ahn Jo, Sangmee;Suk, Kyoungho;Eun, Su-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.219-228
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    • 2015
  • Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

Oxaliplatin-induced Peripheral Neuropathy in Patients with Advanced or Metastatic Gastric Cancer (진행성 또는 전이성 위암 환자에 있어서 Oxaliplatin 투여로 인한 말초신경통증 분석)

  • Park, Ae-Ryoung;Kim, Soon-Joo;Bang, Joon-Seok;La, Hyen-Oh
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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    • pp.18-22
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    • 2009
  • Oxaliplatin is a tolerable and effective drug of choice in the treatment of advanced or metastatic gastric cancer. However, it has many dose-limiting neurotoxicities. This study was performed to assess the incidence and types of oxaliplatin-related neurotoxicities. Sixty-four patients receiving oxaliplatin-involved regimen as salvage therapy on metastatic gastric cancer or as the first-line therapy on advanced gastric cancer were evaluated during the period between September 1, 2006 and February 29, 2008. The patients were treated with oxaliplatin 100 $mg/m^2$ and leucovorin 100 $mg/m^2$ simultaneously as 2-hour-lasting infusion on Day-1 followed by 5-FU 1200 $mg/m^2$ as a 22-hour-lasting continuous infusion both on Day-1 and Day-2 by every other week. We developed questionnaires to evaluate patient-recognized neurotoxic symptoms rather than the observer-described events. Surveys were completed at bedside or via telephone interview. Acute and chronic neurotoxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 3) as well as the Oxaliplatin-specific Neurotoxicity Scale. The Grade-3 neuropathy was reported in 19% of the patients (n=12) and grade-1/2 neuropathy occurred in 70% (n=45). The most common symptom was cold-related dysesthesia (83%) regarded as nociperception by the patients. Some patients (19%) experienced functional impairment affecting activities of daily living such as writing, buttoning, and walking. Even though 74% of the patients (42/57) were prescribed with gabapentin to reduce these peripheral symptoms, it did not appear to derive any benefit from this medication. It is suggested that notify the patients about their oxaliplatin-associated, debilitating symptoms, and educate them any self-care strategy at the initiating phase of the chemotherapy. Moreover, it needs to design the intervention studies regarding the prevention and management of the peripheral neuropathy.

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Neuronal Cell Protective Effects of Methanol Extract from Cheonggukjang Using in vitro System (In vitro system에서 청국장 메탄올 추출물의 신경세포 보호효과)

  • Jeong, Chang-Ho;Kwak, Ji-Hyun;Kim, Ji-Hye;Choi, Gwi-Nam;Jeong, Hee-Rok;Heo, Ho-Jin
    • Korean Journal of Food Science and Technology
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    • v.42 no.6
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    • pp.768-772
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    • 2010
  • In this study, the neuronal cell protective effects of methanol extract from cheonggukjang were evaluated. The proximate composition and total phenolics of the methanol extract were 40.95% crude protein, 22.49% crude fat, 15.99% nitrogen free extract, 7.91% moisture, 6.74% crude ash, 5.92% crude fiber, and 28.43 mg/g of total phenolics. Intracellular ROS accumulation resulting from $H_2O_2$ treatment of PC12 cells was significantly reduced when methanol extract was present in the media compared to PC12 cells treated with $H_2O_2$ only. In a cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide (MTT), the methanol extract showed protective effects against $H_2O_2$-induced neurotoxicity, and lactate dehydrogenase (LDH) release into the medium was also inhibited. Furthermore, the inhibitory effect of the methanol extract against acetylcholinesterase was dose-dependent.

Nutritional Components of Zespri Green Kiwi Fruit (Actinidia delicosa) and Neuronal Cell Protective Effects of the n-hexane fraction (제스프리 그린 키위의 주요 영양성분 및 헥산 분획물의 신경세포 보호효과)

  • Jin, Dong Eun;Kim, Hyeon Ju;Jeong, Ji Hee;Jo, Yu Na;Kwon, O-Jun;Choi, Sung-Gil;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.46 no.3
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    • pp.369-374
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    • 2014
  • The physiological characteristics of kiwi (Actinidia delicosa) fruit were analyzed, which inclued its nutritional composition, in vitro-antioxidant activities, and neuronal cell protective effects. The most abundant components of mineral, amino acid, and fatty acid were found to be potassium (K), glutamic acid, and a-linolenic acid, respectively. The major free sugars were fructose, glucose, and sucrose. In addition, ${\beta}$-carotene and vitamin C contents were $1.35{\mu}g/100mL$ and 29.21 mg/100 g, respectively. The 2,2'-azinobis-(3-ethylbenothiazline-6-sulfonic acid) (ABTS) radical-scavenging activity of the n-hexane fraction obtained from the kiwi extract was 10.52% at a concentration of $1000{\mu}g/mL$. The malondialdehyde (MDA) inhibition of the n-hexane fraction was found to increased in a dose-dependent manner. The intracellular reactive oxygen species (ROS) accumulation after hydrogen peroxide ($H_2O_2$) treatment of PC12 cells was significantly reduced in the presence of the n-hexane fraction compared to PC12 cells treated with $H_2O_2$ only. Moreover, in the a MTT assay, the n-hexane fraction showed in vitro-protective effects against $H_2O_2$-induced neurotoxicity.

Neuronal Cell Protection and Antioxidant Activities of Hot Water Extract from Commercial Buckwheat Tea (시판 메밀차 열수 추출물의 항산화 및 신경세포 보호효과)

  • Jeong, Chang-Ho;Jeong, Hee-Rok;Choi, Sung-Gil;Shim, Ki-Hwan;Heo, Ho-Jin
    • Food Science and Preservation
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    • v.18 no.3
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    • pp.358-365
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    • 2011
  • The antioxidant and neuronal cell-protective effects of hot water extract from commercial buckwheat tea (CBTE) were evaluated. The 2,2'-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, ferric reducing antioxidant power (FRAP), and malondialdehyde (MDA) inhibitory effect of the CBTE increased in a dose-dependent manner. The Intracellular reactive oxygen species (ROS) accumulation that resulted from hydrogen peroxide ($H_2O_2$) treatment more significantly decreased when CBTE was present in the media than when the PC12 cells were treated only with $H_2O_2$. In the neuronal cell viability assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), the aqueous extracts showed a protective effect against $H_2O_2$-induced neurotoxicity, and the lactate dehydrogenase (LDH) release into the medium was also inhibited by CBTE. The total phenolics of CBTE was 9,608.10 mg/100 g, and the major phenolic compounds were rutin (13.42 mg/100 g) and quercitrin (0.90 mg/100 g). These data suggested that CBTE, including the aforementioned phenolics, may be useful in reducing the risk of neurodegenerative disease.

Antioxidant and Neuronal Cell Protective Effects of an Extract of Houttuynia cordata Thunb (a Culinary Herb) (어성초 추출물의 항산화 및 신경세포 보호효과)

  • Jeong, Hee-Rok;Kwak, Ji-Hyun;Kim, Ji-Hye;Choi, Gwi-Nam;Jeong, Chang-Ho;Heo, Ho-Jin
    • Food Science and Preservation
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    • v.17 no.5
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    • pp.720-726
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    • 2010
  • The in vitro antioxidant activities and neuronal cell protective effects of 60% (w/v) methanolic extract from Houttuynia cordata were investigated. The contents of total phenolics and quercitrin in the extract were 17.71 mg/g and 75.80 ${\mu}g$/g, respectively. DPPH and ABTS radical-scavenging activities were 87.79% and 99.27%, respectively, when the extract was tested at 5 mg/ml. The FRAP (ferric reducing/antioxidant power) assay showed a dose-dependent increse in activity. In a cell viability assay using MTT, the extract protected against $H_2O_2$-induced neurotoxicity. Lactate dehydrogenase (LDH) leakage was also inhibited by the extract, as was lipid peroxidation as shown using the mouse brain homogenate test. These data indicate that a 60% (w/v) methanolic extract of Houttuynia cordata has in vitro antioxidant activities, and ingestion there of may reduce the risk of developing neurodegenerative disorders.

Protective effect of ethyl acetate fraction from Actinidia arguta sprout against high glucose-induced in vitro neurotoxicity (포도당으로 유도된 in vitro 뇌신경세포 독성에 대한 다래 순 아세트산에틸 분획물의 보호 효과)

  • Yoo, Seul Ki;Park, Seon Kyeong;Kim, Jong Min;Kang, Jin Yong;Park, Su Bin;Han, Hye Ju;Kim, Chul-Wo;Lee, Uk;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.50 no.5
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    • pp.517-527
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    • 2018
  • The current study investigated in vitro anti-diabetic and neuroprotective effects of the ethyl acetate fraction in Actinidia arguta sprouts (EFAS), on $H_2O_2$ and high glucose-induced cytotoxicity in human neuroblastoma MC-IXC cells. EFAS had high total phenolic and total flavonoid contents. An assessment of 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity of EFAS, as well as its potential for inhibiting malondialdehyde production, indicated that EFAS may possess significant antioxidant properties. EFAS exerted inhibitory effects on ${\alpha}-glucosidase$ via glycemic regulation which forms advanced glycation end products. In addition, EFAS exhibited significant acetylcholinesterase inhibitory effects. Moreover, EFAS displayed protective effects against $H_2O_2$ and high glucose-induced cell death, and inhibited the generation of reactive oxygen species in MC-IXC cells. Finally, the main physiological compound of EFAS was identified via high performance liquid chromatography as a rutin.