• Title/Summary/Keyword: in vivo toxicity

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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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Assessment of Discoidal Polymeric Nanoconstructs as a Drug Carrier (약물 운반체로서의 폴리머 디스크 나노 입자에 대한 평가)

  • BAE, J.Y.;OH, E.S.;AHN, H.J.;KEY, Jaehong
    • Journal of Biomedical Engineering Research
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    • v.38 no.1
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    • pp.43-48
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    • 2017
  • Chemotherapy, radiation therapy, and surgery are major methods to treat cancer. However, current cancer treatments report severe side effects and high recurrences. Recent studies about engineering nanoparticles as a drug carrier suggest possibilities in terms of specific targeting and spatiotemporal release of drugs. While many nanoparticles demonstrate lower toxicity and better targeting results than free drugs, they still need to improve their performance dramatically in terms of targeting accuracy, immune responses, and non-specific accumulation at organs. One possible way to overcome the challenges is to make precisely controlled nanoparticles with respect to size, shape, surface properties, and mechanical stiffness. Here, we demonstrate $500{\times}200nm$ discoidal polymeric nanoconstructs (DPNs) as a drug delivery carrier. DPNs were prepared by using a top-down fabrication method that we previously reported to control shape as well as size. Moreover, DPNs have multiple payloads, poly lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), lipid-Rhodamine B dye (RhB) and Salinomycin. In this study, we demonstrated a potential of DPNs as a drug carrier to treat cancer.

Study a Technique for Reducing the Influence of Scattered Rays from Surrounding Organs to the Heart during Gated Cardiac Blood Pool scan (Gated Cardiac Blood Pool scan에서의 심장 주위 배후방사능 관심영역 설정시 산란선의 영향을 감소시키기 위한 연구)

  • Kim, Jung-Yul;Park, Hoon-Hee;NamKoong, Hyuk;Cho, Suk-Won;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.12 no.1
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    • pp.33-38
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    • 2008
  • Purpose: The Gated cardiac blood pool scan is non-invasive method that a quantitative evaluation of left ventricular function. Also this scan have shown the value of radionuclide ejection fraction measurements during the course of chemotherapy as a predictor of cardiac toxicity. Therefore a reliable method of monitoring its cardiotoxic effects is necessary. the purpose of this study is to minimize the overestimate of left ventricular ejection fraction (LVEF) by modified body position to reduce the influence of scattered rays from surrounding organs of the heart in the background region of interest. Materials and Methods: Gated cardiac blood pool scan using in vivo $^{99m}Tc$-red blood cell (RBC) was carried out in 20 patients (mean $44.8{\pm}8.6$ yr) with chemotherapy for a breast carcinoma. Data acquisition requires about 600 seconds and 24 frames of one heart cycle by the multigated acquisition mode, Synchronization deteriorates toward the end of the cycle and with the distance from the trigger signal (R-wave) by ECG gating. Gated cardiac blood pool scan was studied with conventional method (supine position and the detector head in $30-45^{\circ}$ left anterior oblique position and caudal $10-20^{\circ}$ tilt) and compared with modified method (left lateral flexion position with 360 mL of drinking water). LVEF analysis was performed by using the automatically computer mode. Results: The ROI counts of modified scan method were lower than LV conventional method ($1429{\pm}251$ versus $1853{\pm}243$, <0.01). And LVEF of modified method was also decrease compared with conventional method ($58.3{\pm}5.6%$ versus $65.3{\pm}6.1%$, <0.01). Imaging analysis indicated that stomach was expanded because of water and spleen position was changed to lateral inferior compared with conventional method. Conclusion: This study shows that the modified method in MUGA reduce the influence of scattered rays from surrounding organs. Because after change the body position to left lateral flexion and drinking water, the location of spleen, left lobe of liver and stomach had changed and they could escaped from background ROI. Therefore, modified method could help to minimize the overestimate LVEF (%).

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Current and Future Perspectives of Lung Organoid and Lung-on-chip in Biomedical and Pharmaceutical Applications

  • Junhyoung Lee;Jimin Park;Sanghun Kim;Esther Han;Sungho Maeng;Jiyou Han
    • Journal of Life Science
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    • v.34 no.5
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    • pp.339-355
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    • 2024
  • The pulmonary system is a highly complex system that can only be understood by integrating its functional and structural aspects. Hence, in vivo animal models are generally used for pathological studies of pulmonary diseases and the evaluation of inhalation toxicity. However, to reduce the number of animals used in experimentation and with the consideration of animal welfare, alternative methods have been extensively developed. Notably, the Organization for Economic Co-operation and Development (OECD) and the United States Environmental Protection Agency (USEPA) have agreed to prohibit animal testing after 2030. Therefore, the latest advances in biotechnology are revolutionizing the approach to developing in vitro inhalation models. For example, lung organ-on-a-chip (OoC) and organoid models have been intensively studied alongside advancements in three-dimensional (3D) bioprinting and microfluidic systems. These modeling systems can more precisely imitate the complex biological environment compared to traditional in vivo animal experiments. This review paper addresses multiple aspects of the recent in vitro modeling systems of lung OoC and organoids. It includes discussions on the use of endothelial cells, epithelial cells, and fibroblasts composed of lung alveoli generated from pluripotent stem cells or cancer cells. Moreover, it covers lung air-liquid interface (ALI) systems, transwell membrane materials, and in silico models using artificial intelligence (AI) for the establishment and evaluation of in vitro pulmonary systems.

A Study of the Generation of Transgenic Chickens That Express Human SOD-3 Protein (사람의 SOD-3 단백질을 발현하는 형질전환 닭 생산 연구)

  • Byun, S.J.;Park, C.;Kim, J.A.;Woo, J.S.;Lee, H.C.;Kim, T.Y.;Kim, S.H.;Seong, H.H.;Park, J.K.;Jeon, I.S.
    • Korean Journal of Poultry Science
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    • v.35 no.3
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    • pp.241-245
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    • 2008
  • Lentiviral vector system is efficient vehicles for the delivery of exogenous genes, and it is generally used in the generation of transgenic chickens. In this study, we used recombinant lentiviral vectors to generate transgenic chicks that express the human superoxide dismutase-3 gene driven by the chicken ovalbumin promoter. It is well known that superoxide dismutases(SODs) are believed to play a crucial role in protecting cells against oxygen toxicity. There are three forms of SOD proteins: cytosolic Cu-Zn SOD, mitochondrial Mn SOD, and extracellular SOD(SOD-3). The recombinant lentivirus containing the human SOD-3 gene was injected into the subgerminal cavity of freshly laid eggs. Subsequently, the embryos were incubated to hatch using phases II and III of the surrogate shell ex vivo culture system. From 341 injected embryos, the 78 chicks hatched after 21 days incubation. The hatched chicks were screened for the human SOD-3 gene by using PCR. Two of 47 male chickens that survived to sexual maturity contained the human SOD-3 gene in their semen. These results showed that our transgenic chicken generation system was completely established.

Anti-diabetic Effects of Banaba Leaf Extracts (Lagerstroemia speciosa Pers.) through Solvents (추출용매 변화에 따른 바나바(Lagerstroemia speciosa Pers.) 잎 추출물의 항당뇨 효과)

  • Kim, Kyun-Ha;Roh, Sang-Geun;Li, Chun-Ri;Jin, Chun-Feng;Kim, Andre;Choi, Won-Chul
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1305-1311
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    • 2008
  • This study investigated that the antidiabetic effects of banaba extracts with variety solvents selectivity in vitro and in vivo. Banaba extracts were prepared with water, 70% ethanol, 90% ethanol, 100% ethanol and water-ethanol that of extract twice times sequentially water and ethanol. Cell toxicity and insulin secretion of banaba extracts was tested by MTT (3-[4,5-dimetylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on hamster insulinoma cell line, HIT-T15. Also we tested that insulin, body weight, blood glucose, total cholesterol, HDL-cholesterol, triglyceride and free fatty acid in streptozotocin diabetic rats. Water-ethanol extract has remarkable antidiabetic effect compare with the other banaba extracts. For water-ethanol extract has both of hydrophilic and hydrophobic antidiabetic materials from banaba. Expecially, corosolic acid, as known as unique polyphenol, has antidiabetic effect studied by many researchers till nowadays. But corosolic acid does not solve in water. Otherwise, we suggest that banaba extract of hydrophilic and hydrophobic materials (polyphenol and antioxidants) mixture more increased antidiabetic effects.

Isomeric Folate-Conjugated Polymeric Micelles Bind to Folate Receptors and Display Anticancer Effects

  • Dong, Qing;Xie, Zuo-Xu;Xie, Cao;Lu, Wei-Yue;Zhang, Qian;Li, Xue;Liu, Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7363-7369
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    • 2014
  • The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups for antitumor efficacy. The isomeric block copolymers, ${\alpha}$- and ${\gamma}$-folate-polyethyleneglycol-distearoyl phosphatidylethanolamine (${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPEDOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX, ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both ${\alpha}$- and ${\gamma}$-folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups.

Synthesis and pesticidal activity of ricinine derivatives (Ricinine 유도체(誘導體)의 합성(合成) 및 농약활성(農藥活性))

  • Kwon, Oh-Kyung;Lim, Soo-Kil;Hong, Su-Myeong;Lee, Sung-Eun;Kyung, Suk-Hun
    • The Korean Journal of Pesticide Science
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    • v.2 no.1
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    • pp.24-31
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    • 1998
  • Chemical derivative synthesis of ricinine, an active compound of Ricinus communis which showed high mortality against brown planthopper (Nilaparvata lugens), was performed to improve its pesticidal activity and the toxicity of 12 synthetic derivatives against major insect pests and phytopathogenic fungi were examined. Carbamate derivatives of ricinine could be synthesized from the precursor of ricinine, chloronorricinine and norricinine, whereas the derivatives were not synthesized from chlororicinic acid and ricinic acid having ketone group of pyridine ring. In organophosphates, reaction with oxon type of phosphate gave better yield than thiono type. Among the organophosphate derivatives of ricinine, thiono type of derivative structure gave $96.3%{\sim}100%$ mortality of the brown planthopper and the two-spotted spider mite (Tetranychus urticae) at 500 ${\mu}g/ml$ level. On the other hand, carbamate derivatives did not show insecticidal activity. In the fungicidal activity of ricinine derivatives, the derivative having amino radical at the 2 position of ricinine gave 85 to 100% of mycelium growth inhibition effect against ten major plant pathogens at the 200 ${\mu}g/ml$ level. In particular, the control value of the derivative on the rice blast (Pyricularia grisea) and barley powdery mildew (Erysiphe graminis) at the 250 ${\mu}g/ml$ level in vivo under greenhouse conditions was 92% and 96%, respectively.

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Embryotoxicity and Teratogenicity of Excess Zinc on Xenopus laevis (과량의 아연에 의한 아프리카 발톱개구리 (Xenopus laevis)의 배발생 이상과 독성)

  • Yoon, Chun-Sik;Jin, Jung-Hyo;Cheong, Seon-Woo
    • Korean Journal of Ecology and Environment
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    • v.36 no.1 s.102
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    • pp.83-94
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    • 2003
  • Concentrated releases of zinc into water usually results from discharges associated with industrial purpose. The released zinc into soil is corroded and released into water. In aquatic environment, exess zinc is toxic to the organisms and causes the growth inhibition and malformation of them as a heavy metal. In this study, excess zinc toxicity was tested by FETAX (frog embryo teratogenetic assay with Xenopus)as in vivo system. Xenopus embryos at st.9 were exposed to $100{\sim}900\;{\mu}M$ of zinc for 7 days and 81% of individuals were survived in 100 ${\mu}M$, and 25% were survived in 1000M of zinc solution. In external malformations, swelled belly and intestinal dysplasia were common, and all of tested individuals showed these malformations in 200 ${\mu}M$ or higher concentration of zinc. In 400 ${\mu}M$ or higher concentration, all of tested tadpoles showed faded heart. Also, hypo-pigmentation, lens hernia and loose digestive track were very frequently found in 100 ${\mu}M$ of zinc. The histological study with paraffin section of zinc treated tadpoles showed following abnormalities; regeneration of photoreceptor on retina, reduced vitreous chamber in eye, reduction of red blood cells in heart, abnormal liver, swelling of pronephric cell, muscle dysplasia and palatal papilloma. These abnormalities may be caused by the degeneration of mitochondria, inhibition of cell adhesion, and the formation of leghemoglobin by zinc due to the substitution of $Ca^{2+}$ by $Zn^{2+}$. The body length was reduced due to the excess zinc. From a statistical result, body lengths of 300 ${\mu}M$ or higher concentrative g개ups was significantly reduced comparing that of control group. Recently, many spontaneous malformations and reduction of amphibians are reported, From the results of present study, excess zinc mi호t be a factor of amphibian reduction, and the control of zinc discharges is very important.

Anti-Inflammatory Effect of Ethanol Extract from Onion (Allium cepa L.) Peel on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears (LPS로 유도된 RAW 264.7 세포와 마우스 귀 조직에 대한 양파(Allium cepa L.) 껍질 에탄올 추출물의 항염증 효과)

  • Ahn, Na-Kyung;Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1612-1620
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    • 2015
  • Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.