• Toxicological Research
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• 제27권4호
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• pp.191-203
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• 2011

There has been growing concern about the toxicity of phthalate esters. Phthalate esters are being used widely for the production of perfume, nail varnish, hairsprays and other personal/cosmetic uses. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. The parent phthalate is rapidly metabolized to its monoester (the active metabolite) and also glucuronidated, then excreted. The objective of this study is to evaluate the toxicity of phthalic acid (PA), which is the final common metabolic form of phthalic acid esters (PAEs). The individual PA isomers are extensively employed in the synthesis of synthetic agents, for example isophthalic acid (IPA), and terephthalic acid (TPA), which have very broad applications in the preparation of phthalate ester plasticizers and components of polyester fiber, film and fabricated items. There is a broad potential for exposure by industrial workers during the manufacturing process and by the general public (via vehicle exhausts, consumer products, etc). This review suggests that PA shows in vitro and in vivo toxicity (mutagenicity, developmental toxicity, reproductive toxicity, etc.). In addition, PA seems to be a useful biomarker for multiple exposure to PAEs in humans.

• 약학회지
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• 제43권6호
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• pp.834-842
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• 1999

The metabolism and pharmacokinetics of M-l, which is metabolite of pentoxifylline, have been studied in human liver microsomes. Biphasic kinetics was observed from the Eadie-Hofstee plot for the formation of both metabolites of M-l. For the kinetics of pentoxifylline, mean values of $V_{max1}{\;}and{\;}V_{max2}$ were 1,648 and 5,622 nmol/min/mg protein, and the estimated values of $K_{ml}{\;}and{\;}K_{m2}$ were 0.180 and 4.829 mM, respectively. For M-3, mean values of $V_{max1}{\;}and{\;}V_{max2}$ were 0.062 and 0.491 nmol/min/mg protein, and estimated values of $K_{ml}{\;}and{\;}K_{m2}$ were 0.025 and 1.216 mM. The formations of pentoxifylline and M-3 from M-1 were indentified by using several selective inhibitors of cytochrome P450 isoformes at 0.05-5 mM concentration of M-1 in human liver microsomes. For the analysis of low (0.05 mM) concentration of M-1, where the affinity was expected as low, indicated that CYPlA2 and CYP3A4 were major P450 isoforms responsible for pentoxifylline and M-3 formation. CYP3A4 and CYP2A6 appeared to be P450 isoforms responsible for M-3 formation at high (5 mM) concentration of M-1.

• 대한본초학회지
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• 제27권1호
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• pp.41-49
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• 2012

Objectives : The purpose of this study was to investigate the anti-oxidative and anti-atopic dermatitis effects of persimmon leaf extract obtained from Cheongdo-gun, where more than 60% of Korean persimmon is produced. Methods : Anti-oxidative effects of the crude persimmon leaf extract harvested monthly between May and November were determined by in vitro assay using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide dismutase (SOD)-like reaction. Anti-atopic dermatitis effects of the crude persimmon leaf extract were determined by using collagenase type I inhibition assay and by quantitative assays including serum histamine, prostaglandin E metabolite and leukotriene $B_4$ levels in animal model of atopic dermatitis using Balb/c mice. Results : Persimmon leaf extract harvested in May had higher levels of total phenolic compounds (182.24 mg/g) and flavonoids (23.05 mg/g) than the ones of different month extract. Also, persimmon leaf extract harvested in May showed the most effective extract scavenging activities of DPPH free radical ($13.39{\pm}0.21\;{\mu}g/ml$) and superoxide anion radical ($40.52{\pm}2.32\;{\mu}g/ml$), leading to use the persimmon leaf extract harvested in May for the experiments hereafter. Persimmon leaf extract showed $326.71{\pm}4.6\;{\mu}g/ml$ of 50% inhibitory concentration ($IC_{50}$) for collagenase type I which is responsible for the degradation of extracellular matrix. In addition, persimmon leaf extract application group could decrease serum levels of histamine, prostaglandin E metabolite and leukotriene $B_4$ compared to the negative control in animal model of atopic dermatitis. Especially, persimmon leaf extract showed a significantly decreased serum leukotriene $B_4$ level relative to the levels of histamine and prostaglandin E metabolite. Conclusions : Persimmon leaf extract showed anti-oxidative and anti-atopic dermatitis effects in vitro and in vivo. These results suggest that persimmon leaf extract may have immunoregulatory function for alleviating atopic dermatitis by decreasing collagenase activity and mast cell activation.

• Journal of Ginseng Research
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• 제13권1호
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• pp.42-48
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• 1989

PAH 계 화합물들의 Bay region diol epoxide 들의 target tissue에 대한 결합은 암유발과 관련 되어 있다. 본 논문에서는 ICR mice의 간에서의 BP-DNA-adduct 생성에 미치는 poly acetylene 화합물인 panaxynol 과 panaxydol 의 효과를 조사하였 다. Panaxynol 과 panaxydol 을 전처리한 ICR mice 의 간 마이크로좀을 포함하는 incubation system 은 calf thymus DNA 에 대한 BP binding을 뚜렷이 감소시켰다. [$^3H$]-BP($300\mu$Ci/21nmoles/0.1ml DMSO. i. v. ) 즐 mice 에 주사 후 24시간 후에 간 DNA 에서의 방사능을 측정하였다. HPLC 에 의해 cochromatography 한 두개의 standard marker (acetophenone. bytyrophenone)을 사이에 나타나는 DNA adduct 들을 잠정적으로 확인한 결과 (-) BP-7.8-diol로부터 생성되는 major adduct 인 (+) BP-diol epoxide I: dGuo adduct (peak II)는 대조군보다 약 22% 감소된 반면에 minor adduct 인 (-) BP-diol epoxide I: dGuo adduct (peak III)는 대조군의 69%로 감소되었다. 그리고 (+) BP-7, 8-diol로부 터 생성되는 minor adduct 인 BP-diol epoxide I II : Guo adduct (peak IV)는 대조군의 58%로 감소되었다. 이러한 결과는 panaxydol이 ($\pm$) B BP-7,8-diol로부터 일반적으로 생성되는 adduct들 중 major보다는 minor adduct들의 생성에 더 많이 관석했음을 보여준다.

• Archives of Pharmacal Research
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• 제28권1호
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• pp.100-105
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• 2005

Mancozeb (MCZ) is known to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine peritoneal macrophages through evaluation of MCZ-induced alteration of nitric oxide (NO) production and tumor necrosis $factor-{\alpha}(TNF-\alpha)$ synthesis. Macrophages were examined ex vivo from mice orally treated with various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 $(TNF-{\alpha})$ or 3 days (NO) in the presence of LPS plus $IFN-{\gamma}$. Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 ${\mu}g//mIL$ in the presence of LPS plus $IFN-{\gamma}$ for 2 $(TNF-{\alpha})$ or 3 days (NO) in vitro. NO production was decreased with the in vitro exposure to all concentrations of MCZ. However, the amount of NO production by peritoneal macrophages from MCZ-subacutely exposed mice was increased in comparision with that of control group. In vitro, MCZ suppressed $(TNF-\alpha)$ secretion with significant reduction at 2 ${\mu}g/mL$ MCZ. Conversely, $(TNF-{\alpha})$ release was enhanced ex vivo. This study provides the substantial evidence on MCZ-induced alternation in macrophage activity. In order to clearly understand the contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to further investigate the influence of major metabolite of MCZ (ETU) exposure on the NO production and $(TNF-{\alpha})$ synthesis.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.183-189
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• 2003

General phannacological properties of IH-901, a new pharmacological composition as an intestinal metabolite formed from ginseng protopanaxadiol saponins, were investigated in experimental animals administered orally and in vitro test system. IH-901 had no effects on general behavior, pentobarbital sleeping time, spontaneous motor activity, motor coordination of mice, normal body temperature, chemoshock produced by pentylenetetrazole and writhing syndromes induced by 0.8％ acetic acid at the dose of 25 and 250 mg/kg. Gastric secretion of rats and intestinal motility in mice were not also influenced by the administration of IH-901 at doses of 25 and 250 mg/kg. IH-901 (25 and 250 mg/kg) did not change the mean arterial blood pressure and heart rate in conscious rats. IH-901 had no effect on the respiratory rate at the same doses when it was given to anesthetized rats. In in vitro experiments, IH-90l at the concentration of 25$\mu\textrm{g}$/L did not show any direct effect and inhibitory or augmentative action on the histamine-or acetylcholine-induced contractions in the isolated ileum of guinea-pig. Based on these results, it was concluded that IH-901 did not induce any adverse effects in experimental animals.

• BMB Reports
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• 제47권3호
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• pp.130-134
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• 2014

The combination of a high-affinity antibody to a hapten, and hapten-conjugated compounds, can provide an alternative to the direct chemical cross-linking of the antibody and compounds. An optimal hapten for in vitro use is one that is absent in biological systems. For in vivo applications, additional characteristics such as pharmacological safety and physiological inertness would be beneficial. Additionally, methods for cross-linking the hapten to various chemical compounds should be available. Cotinine, a major metabolite of nicotine, is considered advantageous in these aspects. A high-affinity anti-cotinine recombinant antibody has recently become available, and can be converted into various formats, including a bispecific antibody. The bispecific anti-cotinine antibody was successfully applied to immunoblot, enzyme immunoassay, immunoaffinity purification, and pre-targeted in vivo radioimmunoimaging. The anti-cotinine IgG molecule could be complexed with aptamers to form a novel affinity unit, and extended the in vivo half-life of aptamers, opening up the possibility of applying the same strategy to therapeutic peptides and chemical compounds.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.20-20
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• 2022

Herein, we demonstrate that butein (1) can prevent swelling in a murine lymphedema model by suppressing tumor necrosis factor α (TNF-α) production. Butein derivatives were synthesized and evaluated to identify compounds with in vitro anti-inflammatory activity. Among them, 20 µM of compounds 7j, 7m, and 14a showed 50% suppression of TNF-α production in mouse peritoneal macrophages after lipopolysaccharide stimulation. Compound 14a, exhibited the strongest potency with an in vitro IC₅₀ of 14.6 µM and suppressed limb volume by 70% in a murine lymphedema model. The prodrug strategy enabled a six-fold increase in kinetic solubility of compound 1 and five-fold higher levels of active metabolite in the blood for compound 14a via oral administration in the pharmacokinetics study. We suggest that the compound 14a could be developed as a potential therapeutic agent targeting anti-inflammatory activity to alleviate lymphedema progression.

• 대한화장품학회지
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• 제43권2호
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• pp.137-147
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• 2017

피부의 생태계는 미생물에게 다양한 형태의 서식처를 제공하며, 광범위한 미생물들이 살고 있다. 숙주인 사람은 이들과 공생관계를 이루고 있으며, 이들은 숙주에 많은 긍정적인 영향을 미친다. 피부에 분포하는 미생물들의 다양한 대사물질은 피부세포에 영향을 미치고, 피부장벽 기능, 노화방지 및 항염증에 광범위한 효능을 나타내는 것으로 알려져 있다. 본 연구에서는 사람의 피부에서 신규한 Sporichthyaceae bacterium strain K-07을 분리하였고, 해당 미생물의 16S rRNA 분석결과 Sporichthya속의 미생물과 상동성이 93.4%인 것으로 신규속(genus)으로 확인되었다. 그리고 신규로 분리된 K-07 배양액을 처리하였을 때, HaCaT cell에 어떤 변화가 나타나는지에 대한 분석을 실시하였다. 분리된 신규 미생물 strain K-07의 16S rRNA sequence 분석결과 상동성이 93.4% 이하로 확인되었고, 보고되지 않은 새로운 종으로 확인되었다. Filaggrin, cluadin1, claudin4, ${\alpha}SMase$, 및 CerS3 / HAS3 및 aquaporin3 / IL-6 및 TNF-${\alpha}$ / TSLP 및 TARC를 대상으로 strain K-07 배양액을 처리하여 변화를 관찰하였다. 그 결과 filaggrin, cluadin1, claudin4, ${\alpha}$SMase, 및 CerS3 / HAS3 및 aquaporin3에서는 음성 대조군 대비 우수한 증가 효과가 나타남을 확인하였다. 그리고 IL-6 및 TNF-${\alpha}$ / TSLP 및 TARC에 대해서도 우수한 억제능을 나타내는 것을 확인하였다. 결론적으로 신규 미생물 strain K-07 배양액은 피부 장벽활성 증진에 매우 효과적인 작용을 하며, 염증 억제에 우수한 효능을 나타내는 것으로 확인되므로 피부에 효과적인 소재로 사용될 수 있을 것이다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.565-572
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• 1998

The present study was to evaluate the protective effects of bromocriptine, which is known as $D_2$ dopamine receptor agonist and used for the treatment of patients with Parkinson's disease (PD), on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo. Lipid peroxidation product (malondialdehyde; MDA) produced by the administration of 6-OHDA was profoundly reduced following the treatment of bromocriptine in a dose-dependent manner in rabbit brain homogenate. Quinone formation by 6-OHDA autoxidation was also attenuated, and its effect was as potent as other antioxidants. Pretreatment of bromocriptine reduced the cytotoxicity of 6-OHDA on SH-SY5Y neuroblastoma cell lines dose-dependently. The loss of striatal dopamine and its metabolite, DOPAC (dihydroxyphenylacetic acid) as well as increase of MDA production caused by intrastriatal injection of 6-OHDA was significantly recovered following the treatment of bromocriptine. The present study clearly showed that bromocriptine had a protective action against 6-OHDA-induced neurotoxicity. These results suggest that bromocriptine has the antioxidant properties, which could be another advantage for delaying the progress of Parkinson's disease.