• Title/Summary/Keyword: in vivo toxicity

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Chemical Modification of Chitosan as Gene Carriers In Vitro and In Vivo

  • Kim, Tae-Hee;Jin, Hua;Kim, Hyun-Woo;Cho, Myung-Haing;Nah, Jae-Woon;Cho, Chong-Su
    • Proceedings of the Polymer Society of Korea Conference
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    • 2006.10a
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    • pp.178-178
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    • 2006
  • Chitosan has been investigated as a non-viral vector because it has several advantages such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, low specificity and low transfection efficiency of chitosan as a DNA carrier need to be overcome for clinical trials. In this study, chemical modification for enhancement of cell specificity and transfection efficiency was investigated. Also, the chitosan derivative formulations in vivo were included.

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The Effects of Aristolochic Acid on Reproductive Function in Female Rats (흰쥐에서 아리스톨로킨산이 생식기능에 미치는 영향)

  • Park, Chul-Hoon;Kwack, Seung-Jun
    • Korean Journal of Pharmacognosy
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    • v.40 no.2
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    • pp.89-98
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    • 2009
  • The toxicity of aristolochic acid (ArA) has attracted considerable attention since the case of nephropathy regarding diet pill preparations was reported. The present study was performed to determine the reproductive toxicity of ArA in female SD rats. ArA was administered orally to female rats at 2, 8 or 16 mg/kg b.w./day and the females were mated with untreated males and their reproductive status was determined. ArA is well known as PLA2 inhibitor, toxic effects of such a relationship are not yet clear, and in vivo study on this matter are scarce. For this study, ArA was administered to pregnant rats at 10 or 20 mg/kg b.w./day, because premating treatments were not conducted. Administration of 20 mg/kg b.w./day caused infertility or abortion. In ArA-treated groups, PGF2a productions were inhibited and apoptosis were suppressed. Collectively, this study may help to further define the roles of sPLA2 in reproductive organs and to determine the toxic mechanisms of ArA.

Studies on the Genetic Toxicity of NP-77A

  • Kim, Jai-Hyun;Cho, In-Koo;Park, Kun-Hyuck;Ha, Kwang-Won
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.123-123
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    • 1995
  • To evaluate the genetic toxicity of NP-77A which is selected as the candidate of anti-HBV agent, we performed ames test, micronucleus test, and chromosome aberration test on the CHL cell in vitro. The Ames test was carried out with 5 fold diluted 5 concentrations from 25mg/plate using S. typhimurium and E.coli. After 48hrs incubation, revertant colony numbers was calculated with and without metabolic activation system. In vivo micronucleus test, we investigated the rate of the occurrence of micronucleus after I.P. administration to mice. Andalso, we observed the incidence rate of cells with chromosomal aberration by NP-77A treatment using CHL cell line.

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In vivo Toxicity and Immunoadjuvant Activity of Korean Mistletoe (Viscum album coloratum) Extract Fermented with Lactobacillus (한국산 겨우살이 유산균 발효 추출물의 독성 및 면역증강 효과)

  • Yoon, Taek-Joon;Yang, Woong-Suk;Park, Sung-Min;Jung, Hoe-Yune;Lee, An-Na;Jung, Jin-Hyuk;Kang, Tae-Bong;Yoo, Yung-Choon;Kim, Jong-Bae
    • Korean Journal of Food Science and Technology
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    • v.41 no.5
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    • pp.560-565
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    • 2009
  • In this study, Korean mistletoe extract (KM-110) was fermented with two strains of Lactobacillus (FKM-110) and then toxicity, lectin content, and immune activities were investigated. The lectin content of FKM-110 was about 53-71% lower than that of KM-110. When mice were subcutaneously administered with KM-110 and FKM-110, the $LD_{50}$ obtained for KM-110 treatment was 50-100 mg/kg as compared to 150-200 mg/mL for FKM-110. Each preparation stimulated macrophages directly and enhanced productivity of inflammatory cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. FKM-110 treatment resulted in lower cytokine production compared to KM-110. When mice were immunized with Keyhol limpet hemocyanin (KLH) antigen along with KM-110 or FKM-110 administration, higher antibody titers to KLH were observed in the KM-110 or FKM-110 groups compared to mice immunized with KLH alone, thereby showing no difference between KM-110 and FKM-110. Therefore, fermentation of Korean mistletoe extract with these Lactobacillus strains decreased toxicity in vivo while the enhancement of immune activity by KM-110 and FKM-110 was similar. These data suggest that KM-110 fermentation tended to decrease lectin content and in vivo toxicity. In addition, other components in the fermented mistletoe extract appear to stimulate immuno-adjuvant activity instead of lectin.

Acute Toxicity Assessment in Zebrafish Danio rerio of Arsenic-rich Extracts from Three Species of Seaweeds (제브라피쉬(Danio rerio)를 이용한 비소 고함류 3종 해조류 추출물의 급성 독성평가)

  • Yang, Hye-Won;Kim, Eun-A;Kim, Seo-Young;Jeon, You-Jin
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.51 no.1
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    • pp.31-41
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    • 2018
  • Seaweeds are composed of a variety of bioactive substances, including polysaccharides, pigments, minerals, peptides, and polyphenols. Among these substances, the arsenic content of seaweeds has been a significant cause for concern. The present study evaluated the toxicity of arsenic from three species of seaweed using a zebrafish Danio rerio model. The arsenic-rich extracts were obtained from Ecklonia cava (ECAE), Undaria pinnatifida (UPAE) and Hizikia fusiformis (HFAE) using a solvent of 50% methanol and 1% $HNO_3$. We investigated the toxicity of the arsenic-rich extracts in zebrafish embryos through survival rate, heart rate, yolk sac edema size, cell death, reactive oxygen species (ROS) production and real-time polymerase chain reaction (PCR). The hepatotoxicity of arsenic-rich extracts was assessed in the liver of adult zebrafish through real-time PCR and histopathology. The survival rates of embryos and adult zebrafish showed no significant changes at any concentration. At 100 ppm, embryos did not exhibit significant differences in heart rate, yolk sac edema size, cell death or ROS production. In addition, apoptosis-related genes in larvae and liver tissue were unaffected by treatment with arsenic-rich extracts. These data will help clarify that developmental changes, hepatic oxidative stress, and apoptosis are not associated with toxicity from arsenic-rich seaweed extracts in a zebrafish model.

Reducing effects of taurine on organ toxicity of paraquat

  • Lee, Jeong-Hun;Young, Choung-Se
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.231-231
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    • 1996
  • Paraquat(1.1'-dimethyl-4,4'-bipyridinium ion, PQ)는 전세계적으로 가장 많이 사용되고 있는 농약으로 자살 또는 실수로 마시는 경우 예외없이 폐독성으로 사망하게 된다. 하지만 아직까지 임상에 사용되어지고 있는 효과적인 독성 경감제는 전무한 실정이다. 현재까지 밝혀진 paraquat의 주된 독성기전은 NADPH Cytochrome P$_{450}$ reductase에 의해 산화,환원 반응을 거치는 동안 free radical을 생성하여 세포막에 지질과산화를 일으켜서 세포막의 기능상실과 cell death를 일으킨다고 보고되고 있다. 따라서 본 연구에서는 항산화작용이 뛰어난 아미노산인 taurine(TA)의 radical scarvenging 효과에 의한 PQ 독성경감효과를 in vivo에서 검색하였고, in vitro에서 TA의 PQ 독성경감 mechanism을 밝히고자 하였다. in vivo에서 PQ의 간독성(s-GOT,s-GPT), 신장독성(BUN, Creatinine), 폐 및 전신독성(ALP, MDA, G-6-phosphatase)의 정도를 혈액 및 조직균질액 중에서 검색함으로써 TA의 독성억제효과를 측정하였다.

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Evaluation of the Genetic Toxicity of Synthetic Chemicals(XIV) -In vivo Bone Marrow Micronucleus Assay of 11 Synthetic Chemicals in Mice- (합성화학물질들의 유전독성평가(XIV)-마우스의 골수세포를 이용한 11종 합성화학물질들의 생체내 소핵시험-)

  • Ryu Jae Chun;Kim Youn Jung
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.307-314
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    • 2004
  • 합성화학물질들이 환경으로의 유입은 인체에는 물론 환경생태계에 많은 영향을 미치므로 이들의 유해성 검증은 매우 중요한 일이라 할 수 있다. 실제 산업체에서 사용되는 수많은 화학물질들의 유전적 손상 유발유무는 유해성검증에서 무엇보다 중요한 일이라 할 수 있다. 이에 산업체 공정과정에서 널리 사용되는 것으로 알려진 11종의 합성화학물질에 대해 마우스의 골수 세포를 이용한 in vivo소핵시험을 수행하여, 소핵형성 유발유무를 관찰하였다. 양성대조군으로 사용된 mitomycin C는 음성대조군과 비교시 유의하게 소핵을 유발하는 반면, 비교적 마우스에서 높은 50%치사량을 보이는 thiourea, 2,4-dichlorophenol 및 2,4-toluene diisocyanate 등의 합성물질들을 비롯한 나머지 8종의 물질들은 본 실험결과 통계적으로 유의하게 소핵을 유발하지 않는 것을 관찰 할 수 있었다.

Comparative In Vitro Biological Toxicity of Four Kinds of Air Pollution Particles

  • Shin, Han-Jae;Cho, Hyun Gi;Park, Chang Kyun;Park, Ki Hong;Lim, Heung Bin
    • Toxicological Research
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    • v.33 no.4
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    • pp.305-313
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    • 2017
  • Accumulating epidemiological evidence indicates that exposure to fine air pollution particles (APPs) is associated with a variety of adverse health effects. However, the exact physiochemical properties and biological toxicities of fine APPs are still not well characterized. We collected four types of fine particle (FP) (diesel exhaust particles [DEPs], natural organic combustion [NOC] ash, synthetic organic combustion [SOC] ash, and yellow sand dust [YSD]) and investigated their physicochemical properties and in vitro biological toxicity. DEPs were almost entirely composed of ultrafine particles (UFPs), while the NOC, SOC, and YSD particles were a mixture of UFPs and FPs. The main elements in the DEPs, NOC ash, SOC ash, and YSD were black carbon, silicon, black carbon, and silicon, respectively. DEPs exhibited dose-dependent mutagenicity even at a low dose in Salmonella typhimurium TA 98 and 100 strains in an Ames test for genotoxicity. However, NOC, SOC, and YSD particles did not show any mutagenicity at high doses. The neutral red uptake assay to test cell viability revealed that DEPs showed dose-dependent potent cytotoxicity even at a low concentration. The toxicity of DEPs was relatively higher than that of NOC, SOC, and YSD particles. Therefore, these results indicate that among the four FPs, DEPs showed the highest in vitro biological toxicity. Additional comprehensive research studies such as chemical analysis and in vivo acute and chronic inhalation toxicity tests are necessary to determine and clarify the effects of this air contaminant on human health.

Acute Toxicity Study of Modified Je-Ho-Tang in ICR Mice

  • Lee, In-Sun;Lee, Jeong-Hwa;Han, Jae-ll;Song, Woon-Heung;Kim, Mi-Yeon;Jeon, Won-Kyung
    • Korean Journal of Clinical Laboratory Science
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    • v.44 no.2
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    • pp.59-65
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    • 2012
  • Previous studies have shown that modified Je-Ho-Tang (MJHT) has anti-platelet effects. Je-Ho-Tang (JHT), a Korean court beverage, is a traditional Korean herbal medicine that has been used for the treatment of a disease attended by great thirst, and for prevention of illness in hot summers. We made MJHT from JHT by excluding honey. The present study was performed to determine the acute oral toxicity of crude extract of MJHT in male and female ICR mice. We investigated the in vivo single dose acute toxicity of MJHT hot-water extraction. This test was orally administered once by gavage to 20 mice of each sex received doses of 0 (control group), 1250, 2500 and 5000 mg/kg body weight. Mortalities, clinical findings, autopsy findings and body weight changes were monitored daily for 14 days following the administration. We observed survival rates, general toxicities, changes of body weight, and autopsy. No significant lethality was observed after single oral administration of MJHT at the different dosages. Autopsies on the animals revealed no gross abnormalities. Therefore, the LD50 value of MJHT for ICR mice was estimated more than 5000 mg/kg by the oral route. These results suggest that no toxic dose level of MJHT in mice is considered to be more than 5000 mg/kg. Consequently, it was concluded that MJHT have no effect on acute toxicity and side effect in ICR mice.

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Anti-Oxidant and Hepatoprotective Activities of Ziziphus mucronata Fruit Extract Against Dimethoate-Induced Toxicity

  • Kwape, Tebogo Elvis;Chaturvedi, Padmaja;Kamau, Macharia;Majinda, Runner
    • Journal of Pharmacopuncture
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    • v.16 no.1
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    • pp.21-29
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    • 2013
  • Objective: The study was carried out to evaluate the hepatoprotective and antioxidant potential of Ziziphus mucronata (ZM) fruit extract. Methods: The different types of fruit extract were prepared by soaking the dry powdered fruit in different solvents followed by rotary evaporation. Each extract was tested for its phenol content and antioxidant activities. An in vivo study was performed in Sprague-Dawley (SD) rats. Thirty adult male SD rats (aged 21 weeks) were divided into six groups of five rats each and treated as follows: The normal control (NC) received distilled water while the dimethoate control (DC) received 6 mg/kg.bw.day-1 dimethoate dissolved in distilled water. The experimental groups E1, E2, E3, and E0 received dimethoate (6 mg/kg.bw) + ZMFM (100 mg/kg.bw-1), dimethoate (6 mg/kg.bw) + ZMFM (200 mg/kg.bw-1), dimethoate (6 mg/kg.bw) + ZMFM (300 mg/kg.bw-1), and ZMFM (300 mg/kg.bw-1) only. Both the normal control and the dimethoate control groups were used to compare the results. After 90 days, rats were sacrificed, blood was collected for biochemical assays, and livers were harvested for histological study. Results: High phenol content was estimated, and 2, 2-diphenyl-1-picryl hydrazyl radical (DPPH) spectrophotometric, thin layer chromatography (TLC) and 2, 2-Azobis-3-ethyl benzothiazoline-6-sulphonic acid (ABTS) assays showed a high antioxidant activity among the extracts. The preventive effects observed in the E1, E2 and E3 groups proved that the extract could prevent dimethoate toxicity by maintaining normal reduced glutathione (GSH), vitamin C and E, superoxide dismutase, catalase, cholineasterase and lipid profiles. The preventive effect was observed to be dose dependent. The EO group showed no extract-induced toxicity. Histological observations agreed with the results obtained in the biochemical studies. Conclusion: The study demonstrated that ZM methanol fruit extract is capable of attenuating dimethoate-induced toxicity because of its high antioxidant activity.