• Title/Summary/Keyword: in vitro toxicity

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Amyloid pore-channel hypothesis: effect of ethanol on aggregation state using frog oocytes for an Alzheimer's disease study

  • Parodi, Jorge;Ormeno, David;Paz, Lenin D. Ochoa-de la
    • BMB Reports
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    • v.48 no.1
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    • pp.13-18
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    • 2015
  • Alzheimer's disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer's disease has been the hypotheses of amyloid-pore/channel formation by complex $A{\beta}$-aggregates. Clinical studies suggested the moderate alcohol consumption can reduces probability developing neurodegenerative pathologies. A recent report explored the ability of ethanol to disrupt the generation of complex $A{\beta}$ in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understand how ethanol blocks the aggregation of amyloid. On the other hand, the in silico modeling showed ethanol effect over the dynamics assembling for complex $A{\beta}$-aggregates mediated by break the hydrosaline bridges between Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid pore/ channel hypothesis has been explored only in neuronal models, however recently experiments suggested the frog oocytes such an excellent model to explore the mechanism of the amyloid pore/channel hypothesis. So, the used of frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to explore the mechanism implicates in the Alzheimer's disease pathology and also suggests a model to prevent the Alzheimer's disease pathology.

Kojic Acid Protects C57BL/6 Mice from Gamma-irradiation Induced Damage

  • Wang, Kai;Liu, Chao;Di, Chan-Juan;Ma, Cong;Han, Chun-Guang;Yuan, Mei-Ru;Li, Peng-Fei;Li, Lu;Liu, Yong-Xue
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.291-297
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    • 2014
  • The radioprotective effects of a single administration of kojic acid (KA) against ionizing radiation were evaluated via assessment of 30-day survival and alterations of peripheral blood parameters of adult C57BL/6 male mice. The 30-day survival rate of mice pretreated with KA (75 or 300 mg/kg body weight, KA75 or KA300) subcutaneously 27 h prior to a lethal dose (8 Gy, 153.52 cGy/min) of gamma irradiation was higher than that of mice irradiated alone (40% or 60% vs 0%). It was observed that the white blood cell (WBC) count/the red blood cell (RBC) count, haemoglobin content, haematocrit and platelet count of mice with or without KA pretreatment as exposed to a sub-lethal dose (4 Gy, 148.14 cGy/min) of gamma irradiation decreased maximally at day 4/day 8 post-irradiation. Although the initial WBC values were low in KA300 or WR-2721 (amifostine) groups, they significantly recovered to normal at day 19, whereas in the control group they did not. The results from the cytotoxicity and cell viability assays demonstrated that KA could highly protect Chinese hamster ovary (CHO) cells against ionizing radiation with low toxicity. In summary, KA provides marked radioprotective effects both in vivo and in vitro.

Biocompatibility of Ti-8wt.%Ta-3wt.%Nb alloy with Surface Modification (표면 개질에 따른 Ti-8wt.%Ta-3wt.%Nb 합금의 생체적합성)

  • Lee, Doh-Jae;Lee, Kyung-Ku;Park, Bum-Su;Lee, Kwang-Min;Park, Sang-Won
    • Korean Journal of Materials Research
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    • v.16 no.5
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    • pp.277-284
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    • 2006
  • The alloys were prepared by a non-consumable vacuum arc melting and homogenized at $1050^{\circ}C$ for 24 hrs. Two kind of surface modifications were performed alkali treatment in 5.0M NaOH solution subsequent and heat treatment in vacuum furnace at $600^{\circ}C$, and were oxidizing treatment at the temperature range of 550 to $750^{\circ}C$ for 30 minutes. After surface modification, these samples were soaked in SBF which consists of nearly the same ion concentration as human blood plasma. Cytotoxicity tests were performed in MTT assay treated L929 fibroblast cell culture, using indirect methods. A porous and thin activated layer was formed on Titanium and Ti-8Ta-3Nb alloy by the alkali treatment. A bone-like hydroxyapatite was nucleated on the activated porous surfaces during the in vitro test. However, Ti-8Ta-3Nb alloys showed better bioactive properties than Titanium. According to XRD results, oxide layers composed of mostly $TiO_2$(rutile) phases. Cytotoxicity test also revealed that moderate oxidation treatment lowers cell toxicity and Ti-8Ta-3Nb alloy showed better results compared with Titanium.

Synthesis and Characterization of the Tumor Targeting Mitoxantrone-Insulin Conjugate

  • Liu, Wen-Sheng;Yuan-Huang;Zhang, Zhi-Rong
    • Archives of Pharmacal Research
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    • v.26 no.11
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    • pp.892-897
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    • 2003
  • Anticancer drugs have serious side effects arising from their poor malignant cells selectivity, Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at $37^{\circ}C$ within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1 % of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 $\mu g \cdot$ h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 1l9 h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes ($TI^c$) no larger than 0.3 besides good tumor targeting efficiency with $TI^c$ of 1.67. The results suggest the feasibility to promote the curative effect in ca.ncer chemotherapy by using insulin as the vector of anti-cancer drugs.

Studies on the Yellow Pigment Produced by Monascus sp. CS-2 (Part 3) Safety Test of Yellow Pigment (Monascus sp. CS-2가 생산하는 황색색소에 관한 연구 (제3보) 황색색소의 안전성 시험)

  • Kim, Hyun-Soo;Jang, Wook;Son, Chung-Hong;Bae, Jong-Chan;Yoo, Ju-Hyun
    • Microbiology and Biotechnology Letters
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    • v.9 no.3
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    • pp.117-121
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    • 1981
  • Safety of yellow pigment produced by Monascus sp. CS-2 was evaluated. Acute oral toxicity, pyrogen test, and histamine test, as well as antimicrobial activity were determined. The results obtained were; LD oral in mice was 132.5 mg/20 g, pyrogen test in rabbit was 5 mg/kg, and histamine test in cat was 10 mg/kg. Also the pigment was particularly sensitive to Bacillus subtilis (ATCC 6633), Sarcina lutea (ATCC 9341) and Staphylococcus aureus (ATCC 6538 P), whereas not sensitive to Pseudomonas pyosyanea (ACTC 10490), Bacillus var. mycoides (ATCC 11778), Bordetella bronchiseptica (ATCC 4617) and Staphylococcus epidermidis(ATCC 12228).

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Oxidative Stress in the Cell and Antioxidant Activity of Kalopanax Pictus Extracts (음나무 추출물의 세포 내 산화 스트레스와 항산화 활성)

  • Kim, Sea-Hyun;Park, Youngki;Jang, Yong-Seok;Han, Jingyu;Chung, Hun-Gwan
    • Journal of the Korean Wood Science and Technology
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    • v.35 no.6
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    • pp.126-134
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    • 2007
  • This study reviewed the application of an extract from Kalopanax pictus stem bark and root bark as natural antioxidants. To investigate the effect on cell toxic level against transformed mouse fibroblast L929 in formula added with various extracts from Kalopanax pictus stem bark and root bark, this experiment was carried out by in vitro cytotoxicity method. Using DCFA-DA method, oxidative stress in cell was measured with other antioxidant activity methods including DPPH assay and NBT assay. Active oxygen inhibition rate for root bark insoluble hot water extracts showed the highest with 57.9% for 15 min treatment. In DPPH and NBT test, antioxidant activities of methanol extract from stem bark and insoluble hot water extract from stem bark were 96% (at 0.1%) and 95% (at 0.5%), respectively.

Hydrogel Dressing with a Nano-Formula against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Diabetic Foot Bacteria

  • El-Naggar, Moustafa Y.;Gohar, Yousry M.;Sorour, Magdy A.;Waheeb, Marian G.
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.408-420
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    • 2016
  • This study proposes an alternative approach for the use of chitosan silver-based dressing for the control of foot infection with multidrug-resistant bacteria. Sixty-five bacterial isolates were isolated from 40 diabetic patients. Staphylococcus aureus (37%) and Pseudomonas aeruginosa (18.5%) were the predominant isolates in the ulcer samples. Ten antibiotics were in vitro tested against diabetic foot clinical bacterial isolates. The most resistant S. aureus and P. aeruginosa isolates were then selected for further study. Three chitosan sources were tested individually for chelating silver nanoparticles. Squilla chitosan silver nanoparticles (Sq. Cs-Ag0) showed the maximum activity against the resistant bacteria when mixed with amikacin that showed the maximum synergetic index. This, in turn, resulted in the reduction of the amikacin MIC value by 95%. For evaluation of the effectiveness of the prepared dressing using Artemia salina as the toxicity biomarker, the LC50 was found to be 549.5, 18,000, and 10,000 μg/ml for amikacin, Sq. Cs-Ag0, and dressing matrix, respectively. Loading the formula onto chitosan hydrogel dressing showed promising antibacterial activities, with responsive healing properties for the wounds in normal rats of those diabetic rats (polymicrobial infection). It is quite interesting to note that no emergence of any side effect on either kidney or liver biomedical functions was noticed.

Effect of N-Acetylcysteine on the Supetoxide Release, Chemotaxis from the Neutrophils and Glutathione Level of Plasma and Neutrophils (N-Acetylcysteine이 호중구의 Superoxide, Chemotaxis 및 혈장과 호중구의 Glutathione에 미치는 영향)

  • Song, Jeong-Sup;Lee, Sook-Young;Moon, Hwa-Sik;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.475-483
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    • 1994
  • Background: N-acetylcysteine(ACE) is used both orally and intravenously in a variety of experimental pathologies resembling human disease states which exhibit endothelial toxicity as a result of oxidative stress, including acute pulmonary oxygen toxicity, septicemia and endotoxin shock. Despite these observations in vivo, it is not certain how this thiol drug produces its protective effects. ACE is a cysteine derivative which is able to direct1y react with oxygen radicals and may also act as a cysteine and glutathione(GSH) precursor following deacetylation. In this paper, we tried to know whether the therapeutic doses of ACE can modify the inflammatory function of the neutrophils and can increase the glutathione level of plasma in chronic obstructive pulmonary disease(COPD) patients. In addition, the effect of ACE to the purified neutrophil in terms of superoxide release and glutathione synthesis were observed. Method: Firstly, we gave 600mg of ACE for seven days and compare the release of superoxide, luminol-enhanced chemiluminescence from the neutrophils, neutrophil chemotaxis, and plasma GSH levels before and after ACE treatment in COPD patients. Secondly, we observed the dose dependent effect of ACE to the purified neutrophil's superoxide release and GSH levels in vitro. Results: 1) Usual oral therapeutic doses(600mg per day) of ACE for seven days did affect neither on the neutrophil's superoxide release, chemiluminescence, chemotaxis, nor on the plasma GSH concentration in the COPD patients. 2) ACE decreases the purified neutrophil's superoxide release and increase the GSH production in dose dependent fashion in vitro. Conclusion: Despite the fact that oral ACE treatment did not affect on the neutrophil's inflammatory function and plasma GSH concentration in COPD patients in usual therapeutic doses, it decreases the superoxide release and increases the GSH production from the isolated neutrophils in high molar concentrations. These findings suggest that to obtain an antioxidative effects of ACE, it might be needed to increase the daily dosage of ACE or therapeutic duration or change the route of adminisration in COPD patients.

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In Vitro Stability of Liposomes Containing Newly Synthesized Glycolipid (신규 합성 당지질 함유 리포솜의 In Vitro 안정성)

  • Song, Chung-Kil;Jung, Soon-Hwa;Seong, Ha-Soo;Cho, Sun-Hang;Shin, Byung-Cheol
    • Journal of the Korean Chemical Society
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    • v.51 no.1
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    • pp.43-50
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    • 2007
  • Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.

Antimalarial Activity and Cytotoxicity of Herb-medicine Against P. falciparum in vitro (전통적으로 말라리아 처방에 다용되는 한약재에 대한 항 말라리아 효능과 세포독서에 대한 연구)

  • Kim, Youn-Chul;Kim, Jong-Ho;Park, Hyun;Kim, Yong-Man;Kim, Min-Kyeoung;Jeon, Byung-Hun;Kim, Hye-Sook;Yun, Ki-Jung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.1
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    • pp.102-105
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    • 2005
  • Eighteen methanol extracts of herb-medicine used for malarial and antipyretic therapies in Korea were assessed for their antimalarial activities. Eighteen extracts showed evident antimalarial activity with $EC_50$ values ranged from $2.8\;to\;110mg/m{\ell}$. Evodia fructus showed the antimalarial activity of $EC_50\;=\;4.1\;mg/m{\ell}$ and higher selective toxicity(>8) with no cytotocixity for mammalian cells. This indicated that Evodia fructus is potent for a new effective and safe antimalarial agent. The methanol extract of Physalli radix had also strongest antiplasmodial activity with $EC_50$ value of $2.8{\mu}g/m{\ell}$.