• Title/Summary/Keyword: methotrexate

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Effect of Glutamine on the Methotrexate Induced Gut Barrier Damage, Bacterial Translocation and Weight Changes in a Rat Model (백서에서 Methotrexate에 의하여 유발된 장관장벽손상 및 장내세균전위와 중량 변화에 대한 글루타민의 효과)

  • Kim, Eun-Jeong;Kim, Jeong-Wook
    • YAKHAK HOEJI
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    • v.51 no.1
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    • pp.1-6
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    • 2007
  • The aim of this study was to examine whether administration of glutamine are able to prevent the methotrexate induced gut barrier damage, bacterial translocation, and weight changes. The animals with glutamine were fed with L-glutamine (1.2 and 2.4 mg/kg/day) for 7 days before methotrexate administration (20 mg/kg orally). 48 hour after methotrexate administration, intestinal permeability were measured for an assessment of the gut barrier dysfunction. Also, enteric aerobic bacterial counts, number of gram-negatives in mesenteric lymph node (MLN), liver spleen, kidney and heart were measured for an assessment of the enteric bacterial number and bacterial translocation. Amounts of food intake, body weight changes and organ weight changes of liver spleen, kidney and heart were measured. Methotrexate administration caused body and liver weight loss regardless amounts of food intakes. Methotrexate induced increasing intestinal permeability, enteric bacterial undergrowth and bacterial translocation to MLN, liver and spleen, but not kidney and heart. The supplements with glutamine reduced the intestinal permeability bacterial translocation, and not influences enteric bacterial number, and body and liver weight changes. This study suggested that glutamine might effectively reduce methotrexate induced intestinal damage and bacterial translocation, but not influence body and organ weight loss.

Carbamoyl-phosphate synthetase 2 is identified as a novel target protein of methotrexate from chemical proteomics

  • Kim, Eui-Kyung;Park, Jong-Bae;Ha, Sang-Hoon;Ryu, Sung-Ho;Suh, Pann-Ghill
    • Environmental Mutagens and Carcinogens
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    • v.22 no.4
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    • pp.236-242
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    • 2002
  • Using agarose-coupled methotrexate, we have successfully isolated two proteins, which have strong interactions with methotrexate. The two proteins were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and identified as carbamoyl-phosphate synthetase 2 and phosphoribosylglycinamide formyltransferase, respectively. Interestingly, both of these two proteins are essential key enzymes in nucleotide biosynthetic pathways, like dihydrofolate reductase, a well-known methotrexate target. We confirmed the specificity of their interactions between methotrexate and two target proteins by the methods of competition binding assay, which were followed by western blotting using antibody against carbamoyl-phosphate synthetase 2 and phosphoribosylglycinamide formyltransferase, respectively. Moreover, we could observe that carbamoyl-phosphate synthetase 2 is overexpressed in methotrexate-resistant MOLT-3 cells comparing with control MOLT-3 cells. This result indicates that carbamoyl-phosphate synthetase 2 may be a novel target of methotrexate in cancer therapy. We propose that chemical proteomics can be a powerful technique to identify target proteins of a chemical.

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Cost-Effectiveness Analysis of Etanercept in the Treatment of Methotrexate-resistant Rheumatoid Arthritis (메토트렉세이트 치료에 실패한 류마티스관절염 환자에서 에타너셉트 사용에 대한 비용-효과 분석)

  • Kim Jong-Joo;Park Eun-Ja;Park Se-Jung;Sung Yun-Kyung;Bae Sang-Cheol;Lee Eui-Kyung
    • YAKHAK HOEJI
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    • v.50 no.2
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    • pp.70-77
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    • 2006
  • A cost effective analysis was performed for comparing leflunomide+methotrexate, etanercept monotherapy and etanercept+methotrexate for 6 months. For the patients with methotrexate-resistant RA, ACR20 data were extracted from the published clinical trials searched from Pubmed. The direct medical cost was estimated based on ACR guideline and Korean National Health Insurance reimbursement. Combination therapy of etanercept+methotrexate was found to be more cost-effective than etanercept monotherapy, which meant it was a better therapeutic strategy for methotrexate- resistant RA.

Screening of Methotrexate-Resistant Strains with High Thymidylate Synthase Activity (티미딜산 생성효소 활성이 높은 메토트렉세이트-내성 균주의 검색)

  • Kwak, In-Young;Lee, Jong-Soo
    • YAKHAK HOEJI
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    • v.36 no.4
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    • pp.345-349
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    • 1992
  • Thymidylate synthase activity from extracts of various methotrexate-resistant strains was measured by spectrophotometric assay. Methotrexate-resistant strains of Lactobacillus, Pseudomonas sp., Micrococcus sp. HS-1, Klebsillela pneumonae, Cellulomonas fimi and Serratia marcescens elevated thymidylate synthase levels, especially, Pseudomonas sp. KL-9 resistant to $10^{-9}M$ methotrexate have a 156-fold increase in thymidylate synthase, which suggests that Pseudomonas sp. is a convenient source of thymidylate synthase. Several methotrexate strains of yeast were tested, however, their enzyme activity was generally lower than that of bacteria tested.

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A New Synthetic Studies on Anticancer Agent Methotrexate (Anticancer Agent인 Methotrexate에 대한 새로운 합성 연구)

  • Yu Euy Kyung;Ryu Seoung Ryuall
    • Journal of the Korean Chemical Society
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    • v.37 no.1
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    • pp.136-140
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    • 1993
  • New synthetic method for diethyl N-[4-{[(2,4-diamino-6-yl)methyl]-amino}benzoyl]-L-glutamate(10) which is an intermediate of methotrexate is described. p-Nitrobenzoyl-L-glutamate was obtained via a two-step sequence which involves condensation of p-nitrobenzoyl chloride with diethyl-L-glutamate and Fischer esterification reaction with ethanol. Reductive methylation of diethyl-p-nitrobenzoyl-L-glutamate were carried out by reaction with formic acid and paraformaldehyde in the presence of $PtO_2$ catalyst and yielded diethyl N-(4-methylaminobenzoyl)-L-glutamate(7). It was followed by allylation and iodoazidozation to give the diethyl-p-[N-(2-azido-3-iodopropyl)-N-methyl]aminobenzoyl-L-glutamate(9). The cyclization reaction of compound(9) with 2,4,5,6-tetraaminopyrimidine was carried out by intermolecular nucleophilic substitution to give the desired methotrexate diethylester.

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A Case of Methotrexate Induced Pneumonitis in a Patient with Rheumatoid Arthritis (류마티스 관절염 환자에서 Methotrexate에 의해 발생한 간질성 폐렴 1예)

  • Park, Chan Seok;Lee, Sang Haak;Shim, Kon Ho;Kim, Wan Uk;Lee, Sook Young;Kim, Seok Chan;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.273-277
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    • 2004
  • Methotrexate is commonly used in rheumatoid arthritis as an anti-inflammatory agent, but treatment with methotrexate can lead to severe side effects, especially pulmonary complication. Interstitial pneumonitis is one of the most important pulmonary adverse effects of methotrexate and most patient present with a subacute febrile illness and peripheral eosinophilia is seen in about a half of patients. Almost all patients have abnormal chest roentgenograms and bibasilar interstitial infiltration with alveolar pulmonary consolidations is the most characteristic finding. Interstitial inflammation with mononuclear cell infiltration is a characteristic pathologic feature and findings that suggest acute hypersensitivity pneumonitis, such as bronchiolitis, granuloma formation with giant cells, and infiltration with eosinophils are often present. Methotrexate-induced pneumonitis is a potentially life threatening and unpredictable complication but it is difficult to make a definite diagnosis in the absence of high index of clinical suspicion. Early recognition and appropriate management may avoid the serious outcome. Herein we report a case of methotrexate-induced pneumonitis in a patient with rheumatoid arthritis.

Effect of anticancer drug methortrexate on the biliary excretion kinetics of the reudced folate derivatives in rats (항암제 methotrexate가 랫드 담즙중 환원형엽산유도체의 배설동태에 미치는 영향)

  • Shin, Ho-chul;Cha, Shin-woo;Bae, Ju-hyun;Kim, Hyun-ju;Jeong, Tae-cheon;Park, Jong-il;Yoon, Jong-man;Kim, Gye-woong;Kim, Jin-suk;Han, Sang-seop
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.57-63
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    • 1996
  • The biliary excretion kinetics of the active folate derivatives were examined after an intravenous injection of methotrexate at doses of 0.3 and 10mg/kg to clarify the mechanism of the acute decrease in the plasma folate by the dihydrofolate reductase inhibitors. Even at a higher dose than used in the clinical therapy, methotrexate did not cause any acute depletion of folate denvatives in the excreted bile. Therefore, the decrease in the plasma folate appeared not to be related with the biliary excretion process of folates. A factor responsible for the plasma folate depletion by DHFR inhibitors may be due to the malabsorption of folate derivatives excreted into the small intestine.

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Effects of POLIGONI MULTIFORI RADIX on Imunosuppretion Induced by Methotrexate in Rat (하수오(何首烏)가 methotrexate로 유도된 흰쥐의 면역기능저하(免疫機能低下)에 미치는 영향(影響))

  • Kim Il-Young;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.4 no.2
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    • pp.152-169
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    • 2000
  • To examine the effects of Polygonum multiflorum on white rats with deteriorated immunity caused by methotrexate, first of all, methotrexate was fed to the rats once a day for 4 days. After the immune response of the rats are dereriorated, dried extracts of Polygonum multiflorum mixed in water was fed to the white rats once a day for 144days. The next conclusion was made by examining the rates of B-cells and T-cells of the peripheral blood and the changes in rates of CD4+ T-cells and CD8+ T-cell of the blood sampled from the spleen and peripheral region . Polygonum multiflorum has an effect of increasing immune responses on white rats with deteriorated immunity caused by MTX. Especially the count of CD4+ T-cells of the peripheral blood and the count of CD4+ T-cell of the spleen proved the significant effect o( increasing immune responses statistically . Verification of the effects of the Polygonum multiflorum should be made through comparitive .studies using various immune response indexes. Also additional studies for a modern and practicible application of Polygonum multiflorum seems to be needed.

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