• Title/Summary/Keyword: in vivo toxicity

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The in vitro and in vivo Safety Evaluation of Lactobacillus acidophilus IDCC 3302

  • Bang, Won Yeong;Chae, Seung A;Ban, O-Hyun;Oh, Sangki;Park, Chanmi;Lee, Minjee;Shin, Minhye;Yang, Jungwoo;Jung, Young Hoon
    • Microbiology and Biotechnology Letters
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    • v.49 no.1
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    • pp.39-44
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    • 2021
  • As consumption of healthy foods continues to garner remarkable public attention, ensuring probiotic safety has become a priority. In this study, the safety of Lactobacillus acidophilus IDCC 3302 was assessed in vitro and in vivo. L. acidophilus IDCC 3302 showed negative results for hemolytic and β-glucuronidase activities. The whole-genome analysis (WGA) revealed that L. acidophilus IDCC 3302 did not possess antibiotic resistance or virulence genes. The minimal inhibitory concentrations of L. acidophilus IDCC 3302 confirmed its safety concerning antibiotic resistance. Furthermore, L. acidophilus IDCC 3302 was demonstrated to be nontoxic in the oral toxicity test in rats. Therefore, the results suggested that L. acidophilus IDCC 3302 might be safe for human consumption.

Methylglyoxal Induces Mitochondrial Dysfunction and Cell Death in Liver

  • Seo, Kyuhwa;Ki, Sung Hwan;Shin, Sang Mi
    • Toxicological Research
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    • v.30 no.3
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    • pp.193-198
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    • 2014
  • Degradation of glucose is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Methylglyoxal is produced during glucose degradation and the levels of methylglyoxal are increased in diabetes patients. In this study we investigated whether methylglyoxal induces mitochondrial impairment and apoptosis in HepG2 cells and induces liver toxicity in vivo. Methylglyoxal caused apoptotic cell death in HepG2 cells. Moreover, methylglyoxal significantly promoted the production of reactive oxygen species (ROS) and depleted glutathione (GSH) content. Pretreatment with antioxidants caused a marked decrease in methylglyoxal-induced apoptosis, indicating that oxidant species are involved in the apoptotic process. Methylglyoxal treatment induced mitochondrial permeability transition, which represents mitochondrial impairment. However, pretreatment with cyclosporin A, an inhibitor of the formation of the permeability transition pore, partially inhibited methylglyoxal-induced cell death. Furthermore, acute treatment of mice with methylglyoxal increased the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating liver toxicity. Collectively, our results showed that methylglyoxal increases cell death and induces liver toxicity, which results from ROS-mediated mitochondrial dysfunction and oxidative stress.

Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits

  • Wang, Jie;Zhang, Li;Wang, Lijuan;Liu, Zhonghong;Yu, Yu
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.45-54
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    • 2017
  • Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultra-performance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite $M_{un}$ differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of $M_{un}$ may further suggest an alternative species-specific metabolic pathway.

Scavenging Effects of Flavonoids on Paraquat Induced Toxicity (Paraquat 유독성에 대한 Flavonoid류의 독성경감효과)

  • 최병기;조내규
    • Environmental Analysis Health and Toxicology
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    • v.10 no.1_2
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    • pp.47-54
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    • 1995
  • To investigate and evaluated the scavenging and antioxidative effects of various flavonoids on paraquat induced toxicity, in vivo and vitro tests of eight flavonoids (catechin, epocatechin, flavone, chrysin, apigenin, quercetin, morin and biochanin A) were carried out. The generation of reactive oxygen substances(ROS) in PMS-NADH system $H_2O_2$ induced hemolysis and lipidperoxidation to blood, NADPH dependent lipidperoxidation to liver and lung microsome by paraquat were studied.The results are summerized as follows; 1) In the concentration ranges from 3.3 to 9.8$\mu$M of catechin,epicatechin, quercetin and biochanin A removed the 50% of DPPH radical scavenging effects. 2) In the concentration ranges from 0.60 to 1.86 mM of catechin, epicatechin, quercetin and biochanin A showed the inhibitory and antioxidative activity on superoxide anion which gernerated in PMA-NADH system. 3) In the concentration ranges from 0.12 to 0.49mM of catechin, epicatechin, quercetin and biochanin A showed the inhibitory and antioxidative activity on H202 which generated in PMA-NADH system. 4) In the concentration ranges from 0.6 x10$^{-5}$ to 6.3 x 10$^{-5}$mM of catechin, epicatechin, flavone, chrysin, quercetin and morin showed the inhibitory and antioxidative activity on $H_2O_2$ induced hemolysis to blood 5) All flavonoids tested exhibited inhibitory and antioxidative effects on paraquat induced liver and tung microsomal lipidperoxidation. Therefore, all flavonoids evaluated showed the useful compounds for scavenger and antioxidant on paraquat induced toxicity.

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EVALUATION OF GENETIC TOXICITY FROM ENVIRONMENTAL POLLUTANTS IN DAPHNIA MAGNA AND CHIRONOMUS TENTANS FOR APPLICATION IN ECOLOGICAL RISK ASSESSMENT

  • Park, Sun-Young;Lee, Si-Won;Choi, Jin-Hee
    • Environmental Engineering Research
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    • v.11 no.5
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    • pp.277-284
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    • 2006
  • The genetic toxicity of environmental pollutants, namely, nonylphenol (NP), bisphenol A (BPA) and chloropyriphos (CP) was investigated in aquatic sentinel species, freshwater crustacean, Daphnia magna, and larva of aquatic midge, Chironomus tentans, using Comet assay. Physiological effect of such pollutants was also investigated by studying the specimens' rates of reproduction, growth and survival. Acute toxicity results showed that, as expected, Daphnia was more sensitive than Chironomus to chemical exposure. The order of acute toxicity was CP > NP > BPA in D. magna and NP > CP > BPA in C. tentans. BPA may exert a genotoxic effect on D. magna and C. tentans, given that DNA strand breaks increased in both species exposed to this compound, whereas NP- and CP-induced DNA damage occurred only in C. tentans. In vivo genotoxic data obtained in aquatic sentinel species could provide valuable information for freshwater quality monitoring. The experiments with NP-exposed D. magna showed that the pollutant has long-term effects on reproduction, whereas no short-term effect on DNA integrity was found, being an example of a false-negative result from the biomarkers perspective. This result could be interpreted that other mechanism than genetic alteration might be involved in NP-induced reproduction failure in D. magna. False-positive results from the genotoxic biomarker obtained in BPA-exposed D. magna and in NP-exposed C. tentans make it difficult to use DNA integrity as an early warning biomarker. However, as the mere presence of genotoxic compounds, which are potentially carcinogenic, is of high concern to human and ecosystem health, it could also be important to rapidly and effectively detect genotoxic compounds in the aquatic system in ways that do not necessarily accompany a higher level of alteration. Considering the potential of D. magna and C. tentans as bioindicator species, and the importance of genotoxic biomarkers in ecotoxicity monitoring, DNA damage in these species could provide useful information for environmental risk assessment.

Study on Kidney Toxicity of BDR-29 for Treatment Vascular Diseases in Rats (혈관질환 억제 효능이 있는 BDR-29의 백서 신장 독성연구)

  • Kim, Eun-Ju;Kang, Dae-Gill;Lee, An-Sook;Choi, Deok-Ho;Cho, Kuk-Hyun;Kim, Sung-Yun;Lee, Ho-Sub
    • Herbal Formula Science
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    • v.16 no.2
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    • pp.163-169
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    • 2008
  • The kidney toxicities of BDR-29 used for improvement of the vascular diseases, was examined using male and female Sprague-Dawley rats. The male and female rats were divided into 4 groups for intragastrical treatment with doses of 0, 5, 50, and 500 mg/kg/day for 13 weeks, respectively. In all male and female rats treated with BDR-29, no mortality and gross pathological findings were shown for 13 weeks. There substantially was no change in body weight in all rats with treatment of BDR-29. The renal functional parameters including urinary volume, urine osmolality, electrolytes excretory rate, creatinine clearance, and solute-free water reabsorption were not exchanged in all rats treated with BDR-29. Taken together, these results suggest that BDR-29 has no toxicity on kidney in all male and female rats.

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Whitening Effect of Octaphlorethol A Isolated from Ishige foliacea in an In Vivo Zebrafish Model

  • Kim, Kil-Nam;Yang, Hye-Mi;Kang, Sung-Myung;Ahn, Ginnae;Roh, Seong Woon;Lee, WonWoo;Kim, Daekyung;Jeon, You-Jin
    • Journal of Microbiology and Biotechnology
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    • v.25 no.4
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    • pp.448-451
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    • 2015
  • In a previous study, we isolated octaphlorethol A (OPA) from Ishige foliacea and evaluated its anti-melanogenesis activity in a murine melanoma cell line. However, the whitening effect and toxicity of OPA have not yet been examined in vivo. Therefore, in this study, we investigated the inhibitory effect of OPA on melanin synthesis and tyrosinase activity in an in vivo zebrafish model. More than 90% of subject embryos survived upon exposure to OPA concentrations below $25{\mu}M$, which was not significantly different from the finding in the control group. OPA markedly inhibited melanin synthesis and tyrosinase activity in a concentration-dependent manner.

Studies on the Bis (amino-alkyl-oxo) Oxalate Derivatives As a Antidote of Lead poisoning (Bis (\beta$-amino-alkyl-oxo) oxalate 유도체의 납 중독 해독에 관한 연구)

  • 최선아;유미례;노영수;정성현;정세영
    • Environmental Analysis Health and Toxicology
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    • v.4 no.3_4
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    • pp.1-6
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    • 1989
  • The effects of his ($\beta$-amino-ethyl-oxo) oxalate and bis ($\alpha$-amino-methyl-oxo) oxalate on the toxicity of lead acetate in rast were examined. Rats were given intraperitoneally at the dose of lead acetate 45 mg/kg. The exposure of lead acetate showed the 70% decrease of ALAD ($\delta$-amino levulinic acid dehydratase) activity in red blood cell. In vivo 122 mg/kg administration of bis ($\beta$-amino-ethyl-oxo) oxalate and bis ($\alpha$-amino-methyl-oxo) oxalate showed the 50% increase of ALAD activity, whereas 149 mg/kg administeration of Ca-EDTA had no effect. In vitro, the same results were obtained. Both compounds had hemolytic activity at concentrations higher than that required for showing the 50% ALAD activity increase in vivo.

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Toxicity and Biomedical Imaging of Fluorescence-Conjugated Nanoparticles in Hematopoietic Progenitor Cells

  • Min, Gye-Sik;Kim, Dong-Ku
    • Reproductive and Developmental Biology
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    • v.35 no.4
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    • pp.503-510
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    • 2011
  • Cellular uptake of nanoparticles for stem cell labeling and tracking is a critical technique for biomedical therapeutic applications. However, current techniques suffer from low intracellular labeling efficiency and cytotoxic effects, which has led to great interest in the development of a new labeling strategy. Using silica-coated nanoparticles conjugated with rhodamine B isothiocyanate (RITC) (SR), we tested the cellular uptake efficiency, biocompatibility, proliferation or differentiation ability with murine bone marrow derived hematopoietic stem/progenitor cells. The bone marrow hematopoietic cells showed efficient uptake with SR with dose or time dependent manner and also provided a higher uptake on hematopoietic stem/progenitor cells. Biocompatibility tests revealed that the SR had no deleterious effects on cell cytotoxicity, proliferation, or multi-differentiation capacities in vitro and in vivo. SR nanoparticles are advantageous over traditional labeling techniques as they possess a high level of cellular internalization without limiting the biofunctionality of the cells. Therefore, SR provides a useful alternative for gene or drug delivery into hematopoietic stem/progenitor cells for basic research and clinical applications.

Long arm octopus (Octopus minor) extract prevents eye injury caused by particulate matter exposure in zebrafish (Danio rerio) embryos

  • Thilini Ranasinghe;Seon-Heui Cha
    • Fisheries and Aquatic Sciences
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    • v.27 no.2
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    • pp.111-121
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    • 2024
  • Particulate matter (PM) is a mixture of microscopic solid inhalable particles including airborne liquid droplets, and it is implicated with several diseases. The eye does not have a protective barrier among the human organs, consequently it get directly exposed to environmental substances such as PM. The scarcity of treatments for damage to the eyesight and the vision and eye structure being closely related to the structure and function of the central nervous system highlights the cruciality of novel therapeutics. In this study was conducted using in vivo zebrafish vertebrate model which is a useful model due to the conserved genes between human. We found that protective effect of Octopus minor extract against particulate matter-induced adverse effects on eye development in zebrafish (Danio rerio) embryos by regulating antioxidant and anti-inflammatory mRNA expression.