• Parasites, Hosts and Diseases
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• 제54권2호
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• pp.155-161
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• 2016

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.

• 대한약리학회지
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• 제21권1호
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• pp.34-48
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• 1985

항균제 nitrofurantion에 의한 폐독작용의 생화학적 기전을 규명하기 위한 연구 일환으로 in vitro에서 폐장 microsome 지질의 과산화 및 반응성 산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2,\;OH{\cdot},\;^1O_2)$의 생성에 대한 nitrofurantion의 영향과 양자 간의 상호 관련성을 검토하였다. Nitrofurantion은 호기성 반응 조건에서 돼지 폐장 microsome의 NADPH 의존성 지질 과산화를 용량 의존적으로 증가시킬 뿐 아니라 $O^{-}_{2}{\cdot},\;H_2O_2$ 및 두 radical의 상호 작용으로 2차적으로 형성되는 $OH{\cdot}$의 생성 또한 촉진하였으며 $^1O_2$생성은 관찰되지 않았다. 이와 같은 폐장 microsome지질 과산화 증가는 SOD 및 catalase에 의하여 억제될 뿐만 아니라 $OH{\cdot}$ 제거 물질인 mannitol, thiourea에 의하여도 현저히 억제되었으며, $^1O_2$ 제거 물질에 의하여는 영향을 받지 않았던 한편 염기성 반응 조건에서는 nitrofurantoin에 의한 지질 과산화가 관찰되지 않았다. 이상의 결과로 미루어 보아 nitrofurantoin은 폐장 microsome의 NADPH 의존적이 반응성산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2$ 및 $OH{\cdot})$의 생성을 증가시키며 이들 중 특히 $OH{\cdot}$ 에 의한 microsome막 지질 과산화를 촉진하는 것으로 결론지었고, 이와 같은 in vivo 현상은 nitrofurantion의 in vitro 폐독작용의 기전을 설명하는 일부가 될 것으로 사료하였다.

• 생약학회지
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• 제40권2호
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• pp.137-142
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• 2009

Isoniazid was discovered in 1950's and since then it has been widely used as a synthetic bactericidal agent in the treatment of tuberculosis. However, the adverse effect of isoniazid has been reported to show significant hepatotoxicity in approximately 1-2% of patients. Nitrofurantoin {1-(5-nitro-2-furfurylideneamino)-hydantoin} is a synthetic nitrofuran that is commonly used for the treatment and prophylaxis of urinary tract infections, but its use is associated with liver cirrhosis and fatal liver necrosis. Therefore, studies for natural products with protective effect on the isoniazid- and/or nitrofurantoin-induced hepatotoxcity would be valuable as the potential therapeutic use. 107 plants sources were collected at Mt. Baekdu, and extracted with methanol. These extracts had been screened for the protective effects against isoniazid- and/or nitrofurantoin-induced cytotoxicity in HepG2 cells at the both 100 and $300{\mu}g/ml$. Five methanolic extracts, Acanthopanax senticosus, Acer mono, Asparagus schoberioides, Fagopyrum tataricum, Potentilla centigrana, showed significant protective effects against isoniazidinduced hepatotoxicity. Two methanolic extracts, Acer mono and Leonurus artemisia, showed significant protective effects against nitrofurantoin-induced cytotoxicity in HepG2 cells.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.222-230
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• 2007

Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. Nitrofurantoin (NF) is clinical chemotherapeutic agent and antimicrobial and used to treatment of urinary tract infections. However, NF has been shown to result in pulmonary toxic effects. In this research, we revealed the changing expression gene profiles in BEAS-2B, human bronchial epithelial cell line, exposed to NF by using human oligonucleotide chip. Through the clustering analysis of gene expression profiles, we identified 136 up-regulated genes and 379 down-regulated genes changed by more than 2-fold by NF. This study identifies several interesting targets and functions in relation to NF-induced toxicity through a gene ontology analysis method including biological process, cellular components, molecular function and KEGG pathway.

• 한국가금학회지
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• 제7권1호
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• pp.53-64
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• 1980

A total of 1503 specimens were submitted to the Poultry Disease Diagnostic Service Laboratory during the year 1966 and 1978. The most frequently diagnosed diseases in order of prevalence were avian mycoplasmosis, staphylococcosis, colibacillosis, salmonellosis and pullorum disease, the percentages of the conditions being 24.6%, 20.0%, 18.0%, 12.6% and 6.4%, respectively, The drug resistance of pathogenic mirnoorganisms isolated during the year 1978 from chicken with colicabacillosis, staphylococcosis or salmonellosis were investigated by the use of disc diffusion technique, the results being as follow. 1) Drug resistance of 63 strains of Escherichia coli More than 95% of the strains tested were sensitive to colistin and gentamicin. The percentages of strains sensitive to kanamycin, chloramphenicol, ampicillin and nitrofurantoin were 66.7%, 60.3%, 60.3% and 47.6%, respectively. Majority of the strains were highly resistant to streptomycin and tetracyline. All the strains were resisistant to bacitracin lincomycin, oleandomycin, penicillin and erythromycin. All the strains tested were resistant to more than two among 10 drugs in common use such as penicillin, erythromycin, streptomycin, tetracycline, neomycin, chloramphenicol, kanamycin, ampicillin and gentamicin, and 27 different resistance patterns were noted. The most frequent multiple resistance pattern was PC, EM, SM and TC (11.1%). 2) Drug resistance of 48 strains of Salmonella More than 95% of the strains tested were sensitive to colistin, gentamicin ana ampicillin. The percentages of st rains sensitive to kanamycin, tetracycline, neomycin and nitrofurantoin were 81,3%, 79%, 72.9%, and 68.0% respectively. None of them was sensitive to streptomycin, oleandomycin, erythromycin, lincomycin and bacitracin. All the strains were resistant to more than one among 7 drugs in common use such as streptomycin, erythromycin, neomycin, tetracycline, kanamycin, ampicillin and gentamicin. The most frequent resistance pattern was SM and EM(66.7%). 3) Drug resistance of 54 strains of Staphylococci All the strains tested were sensitive to gentmaicin, kanamycin and cephalothin. Majority of them were highly sensitive to bacitracin, methicillin, nitrofurantoin and chloramphenicol. The Percentages of strains sensitive to streptomycin, ampicillin, lincomycin and tetracycline were 66.7%, 55.6%, 44.4% and 27.8%, respectively. Among them, 51 strains were resistant to more than one among 11 drugs in common use such as tetracycline, lincomycin, ampicillin, penicillin, streptomycin, erythromycin, neomycin, oleandomycin, chloramphenicol, methicillin and bacitracin, and thirty one different resistance patterns were noted.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.528-532
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• 2008

소아에서 약물 유발성 독성 간염은 비교적 흔하며 대부분 약을 끊으면 호전된다. 특히 항결핵약은 주요 유발 약물이다. 약물 유발성 독성 간염은 자가면역질환을 동반할 수 있으며, 이러한 원인으로 보고된 약제로는 주로 methyldopa, nitrofurantoin, minocycline, interferon 등이고, 항결핵약 보고는 드물다. 저자들은 갑상선염이 동반되고 항결핵약 isoniazid와 rifampin으로 유발된 약물 유발성 자가면역간염을 경험하였기에 국내에서 처음으로 문헌고찰과 함께 보고하는 바이다.

• 미생물학회지
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• 제14권4호
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• pp.151-158
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• 1976

Using Ames'Salmonella/microsome system, mutagenicity of antirichomonal nitrofuran, nitroimidazole, and nitrothiazole derivatives was examined. Nitrofurantoin, nifuratel, furazolidone, metronidazole, nimorazole, ornidazole, and aminitrozole showed potent mutagenicity en $TA_100$ strain which is a base substitute mutant and contains R-factor plasmid pKM101 without microsomal enzyme activation. In addition, nifuratel, furazolidone, metronidazole, and ornidazole also induced frameshift mutation in $TA_98$ strain.

• 대한미생물학회지
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• 제7권1호
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• pp.1-8
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• 1972

The authors made a study on the bacteriological identification about unidentified strains which were roughly screened by local health center, which an epidemic diarrhea was outbreak at Ham Yang Gun, Kyeongsang-Namdo in July 1971. And the authors made an attempt to bacteriological Identification, serotyping with slide agglutination, and determination of the susceptibility of identified strains to various chemotherapeutic agents. The results Were obtained as follows: 1. The isolated strains identified Shigella flexneri type 2b(2 strains) and Salmonella paratyphi B(4 strains). 2. Sensitivity test using with three concentrations chemotherapeutic agents(Paper disk used; Eiken chemical Co., Tokyo, Japan): (1) Shigella flexneri type 2b isolated strains were sensitive to kanamycin, colistin(100%) and penicllin(50%) respectively, but resistant to erythromycin, oleandomycin, leucomycin, chloramphenicol, tetracycline, dihydrostreptomycin and sulfadimethoxin(100%) respectively. (2) Salmonella paratyphi B isolated strains were sensitive to chloramphenicol, tetracycline, dihydrostreptomycin, kanamycin, sulfadimethoxine(100%) and colistin(50%) respectively, but resistant to penicillin, erythromycin, oleandomycin and leucomycin(100%) respectively. 3. Sensitivity test using with multodisk urinary code(Paper disk used; Oxoid, London): (1) Shigella flexneri type 2b isolated strains were sensitive to Bactrim, ampicillin, nitrofurantoin, nalidixic add and gentamicin(100%) respectively, but resistant to chloramhpenicol, tetracycline, sulfadiazine and Fanasil(100%) respectively. (2) Salmonell paratyphi B isolated strains were sensitive to Bactrim, chloramphenicol, ampicillin, nitrofurantoin, tetracycline, nalidixic acid, gentamicin(100%) and sulfadiazine(50%) respectively, but resistant to Fanasil(100%) and sulfadiazine(50%) respectively.

• 대한미생물학회지
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• 제10권1호
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• pp.13-17
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• 1975

저자들은 1967년 이래 '71년, 72년, 73년 4년에 걸쳐 232주의 전형적인 이질균을 동정확인하여 정리한바 있다. 1974년에도 1,504주의 장내 병원성세균이 각 시, 도, 위생시험소 및 종합병원 등에서 수집되어 검사대상이 되었으며 이질균으로 동정확인된 47주를 얻게 되었으므로 그들의 미생물학적 성상을 보고하는 바이다. 서울에서 분리된 shigella flexneri 3주를 제외하고는 강원도에서 44주가 분리되었으며, 그 내역은 sihgella dysenteriae가 1주, shigella flexneri가 43주, shigella sonneri가 3주이었다. 생물학적 성상중 과거에 시험되지 않았던 Christensen's citrate, Sodium acetate, Sodium alginate, Esculin test 등을 시도하였으며 그결과는 미국 Center for Disease Control에서 발표된 성적과 비슷한 결과로 나타났다. 우리나라에서 흔히 상용될 수 있는 항생제에 대한 감수성 검사를 실시하였으며 nitrofurantoin, cephalosporin, ampicillin, penicillin G $1{\mu}g$에 대해서는 1973년도 균주와 마찬가지로 감수성균으로 반응을 보였으며, 반대로 bacitracin, lincomycin, penicillin V $10{\mu}g$에 대해서는 전적으로 내성이 있는 것으로 나타났다. 이 결과들은 예년과 마찬가지로 Ericsson씨 법에 의해 관찰된 것이었다.

• BMB Reports
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• 제32권2호
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• pp.127-132
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• 1999

The NAD(P)H-quinone oxidoreductase (EC 1. 6. 99. 2) was purified from S. cerevisiae. The native molecular weight of the enzyme is approximately 111 kDa and is composed of five identical subunits with molecular weights of 22 kDa each. The optimum pH of the enzyme is pH 6.0 with 1,4-benzoquinone as a substrate. The apparent $k_m$ for 1,4-benzoquinone and 1,4- naphthoquinone are 1.3 mM and $14.3\;{\mu}M$, respectively. Its activity is greatly inhibited by $Cu^{2+}$ and $Hg^{2+}$ ions, nitrofurantoin, dicumarol, and Cibacron blue 3GA. The purified NAD(P)H-quinone oxidoreductase was found capable of reducing aromatic nitroso compounds as well as a variety of quinones, and can utilize either NADH or NADPH as a source of reducing equivalents. The nitroso reductase activity of the purified NAD(P)H-quinone oxidoreductase is strongly inhibited by dicumarol.