• Title/Summary/Keyword: Metabolic activation

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Genotoxic Evaluation of Surfactin C in Chinese Hamster Lung Cell Line

  • Lim, Jong-Hwan;Song, In-Bae;Park, Byung-Kwon;Kim, Myoung-Seok;Hwang, Youn-Hwan;Yun, Hyo-In
    • Toxicological Research
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    • v.25 no.1
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    • pp.47-50
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    • 2009
  • To investigate the mutation inducibility of surfactin C, we performed the chromosome aberration assay with Chinese hamster lung cells in vitro. The colorimetric MTT screening assay was carried out to determine the cytotoxicity index ($IC_{50}$) of surfactin C. The $IC_{50}$ value was $125{\mu}g/ml$. For the chromosome aberration test of surfactin C, the maximum concentration was employed as $125{\mu}g/ml$, followed by 62.5 and $31.25{\mu}g/ml$ for the lower concentrations, with or without metabolic activation (S9). Cyclophosphamide and mitomycin C were used as positive controls in the presence and absence of S9 metabolic activation, respectively. These results showed that surfactin C was not capable of inducing chromosome aberration, as measured by the chromosome aberration test using Chinese hamster lung cell line. There is no evidence for surfactin C to have a genotoxic potential.

Effects of Chrysene on the Immune Functions in Female BALB/c Mice (Chrysene이 BALB/c계 마우스의 면역기능에 미치는 영향)

  • Jeon, Tae-Won;Kim, Chun-Hua;Lee, Sang-Kyu;Kim, Ghee-Hwan;Jun, In-Hye;Lee, Dong-Ju;Jeong, He-Min;Jeong, Tae-Cheon
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.244-253
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    • 2006
  • Effects of chrysene on immune functions were studied in female BALB/c mice. When mice were treated po with chrysene for 7 consecutive days, the antibody response was suppressed dose-dependently. Chrysene induced the enzyme activities of CYP LA and 2B time- and dose-dependently. In ex vivo lymphocyte proliferation, chrysene inhibited splenocyte proliferation by LPS and Con A. Moreover, the numbers of $CD4^+IL-2^+$ cells were reduced by chrysene. In conclusion, chrysene-induced immunotoxicity might be mediated, at least in part, via IL-2 production, and caused by mechanisms associated with metabolic activation.

Evaluation of Genotoxicity of SU-Eohyeol Pharmacopuncture Using an In Vitro Chromosome Aberration Test in Chinese Hamster Lung Cell

  • Ku, Jaseung;Hwang, Ji Hye
    • Journal of Pharmacopuncture
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    • v.25 no.3
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    • pp.290-300
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    • 2022
  • Objectives: This study was conducted to evaluate the safety of SU-Eohyeol pharmacopuncture (SUEP) by assessing its potential to cause chromosomal abnormalities in Chinese hamster lung cells (CHL/IC). Methods: A dose-curve was conducted to determine the highest dose of SUEP. Doses of 10, 5, 2.5, 1.25, 0.625, and 0.313% were used, and no cytotoxicity or SUEP precipitation was observed. SUEP doses of 10, 5, and 2.5%, with positive and negative controls, were used in a chromosome aberration test. Results: In this study, the frequency of abnormal chromosomal cells in the SUEP group did not show a statistically significant difference from that of the negative control group in short-term treatments with and without metabolic activation and the continuous treatment without metabolic activation. Compared with the negative control group, the positive control group had a significantly higher frequency of cells with structural chromosomal abnormalities. This test's results satisfied all conditions for determining the results. Conclusion: SUEP did not induce chromosomal aberrations under the conditions of this study. Other toxicity evaluations, safety studies in humans, and various clinical trials are required to evaluate the safety and efficacy of SUEP.

Genotoxicity Evaluation Using Reversion Mutation Test of SU-Eohyeol Pharmacopuncture (SU어혈약침의 복귀돌연변이시험을 이용한 유전독성평가)

  • Ku, Jaseung;Hwang, Ji Hye
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.36 no.4
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    • pp.113-119
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    • 2022
  • SU-Eohyeol pharmacopuncture(SUEP) was developed by adding Cervi Pantotrichum Cornu to Jungsongouhyul pharmacopuncture. This genotoxicity evaluation was performed to evaluate the mutagenic potential of the test substance SUEP agent using histidine, which requires strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537), and tryptophan, which requires Escherichia coli (WP2uvrA) strain in the presence and absence of metabolic activation. According to the results of the dose range finding study conducted prior to the main study, the dose levels of the test substance in the main study were determined as 100, 50, 25, 12.5, 6.25%, and positive and negative controls were established. As a result of the main study, the mean number of revertant colonies compared to negative controls was less than 2-fold at all dose levels of SUEP in all strains with and without metabolic activation. In the positive control group, the mean number of revertant colonies for each strain was markedly increased by more than two times compared to the negative control group. Based on the result of this study, the test substance, SUEP did not show any indication of mutagenic potential under the conditions of this study.

Metabolism-based Anticancer Drug Design

  • Kwon, Chul-Hoon
    • Archives of Pharmacal Research
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    • v.22 no.6
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    • pp.533-541
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    • 1999
  • Many conventional anticancer drugs display relatively poor selectivity for neoplastic cells, in particular for solid tumors. Furthermore, expression or development of drug resistance, increased glutathione transferases as well as enhanced DNA repair decrease the efficacy of these drugs. Research efforts continue to overcome these problems by understanding these mechanisms and by developing more effective anticancer drugs. Cyclophosphamide is one of the most widely used alkylating anticancer agents. Because of its unique activation mechanism, numerous bioreversible prodrugs of phosphramide mustard, the active species of cyclophosphamide, have been investigated in an attempt to improve the therapeutic index. Solid tumors are particularly resistant to radiation and chemotherapy. There has been considerable interest in designing drugs selective for hypoxic environments prevalent in solid tumors. Much of the work had been centered on nitroheterocyclics that utilize nitroreductase enzyme systems for their activation. In this article, recent developments of anticancer prodrug design are described with a particular emphasis on exploitation of selective metabolic processes for their activation.

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Dynamic Modeling of Lactic Acid Fermentation Metabolism with Lactococcus lactis

  • Oh, Euh-Lim;Lu, Mingshou;Choi, Woo-Joo;Park, Chang-Hun;Oh, Han-Bin;Lee, Sang-Yup;Lee, Jin-Won
    • Journal of Microbiology and Biotechnology
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    • v.21 no.2
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    • pp.162-169
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    • 2011
  • A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

The relationship between workers health behaviorals, oral health behaviorals and metabolic syndrome risk factors periodontal disease status (근로자의 건강 행태, 구강건강 행태 및 대사증후군 위험요인과 치주질환과의 관련성)

  • Ku, In-Young;Kim, Han-Gon
    • Journal of Korean society of Dental Hygiene
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    • v.12 no.3
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    • pp.597-609
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    • 2012
  • Objectives : The purpose of this study was to determine the influence of workers health behaviorals, oral health behaviorals and metabolic syndrome risk factors on oral health and to identify the relationship between these. and then, a basis data propose for integrative health promotion programs development and effective Management measures. Methods : The subjects were 4,600 workers working at a industrial place in North Gyeongsang Province, data were collected from July 13, 2010 to September 12, 2010. using the results of the subjects medical check-ups and Oral examinations, this study was performed. collected data included workers general characteristics, job characteristics, and smoking, drinking, exercise behavior as lifestyle factors, and waist measurement, fasting blood sugar level, systolic blood pressure, diastolic blood pressure, the level of Triglyceride and HDL-cholesterol as metabolic syndrome risk factor indicator. Data were analyzed by descriptive statistics, chi-square test, correlation analysis, logistic regression using SPSS 18.0. Results : In results of the subjects medical check-ups, 14.1% were above the criterion value of waist measurement, 2.5% fasting blood sugar level, 8.5% hypertension, 16.8% Triglyceride level and 4.0% HDL-cholesterol respectively. according to oral examination results, showing that 43.3% inflammation of the gums. The inflammation of the gums was correlated with gender, age, dental clinic visit, scaling management, smoking, exercise behavior and high triglyceride level and hypertension of metabolic syndrome risk factor indicators. In addition, this result was statistically significant. Conclusions : Based on this study, the workers health should be managed actively and effectively by using periodical workers health check-ups. At a corporate level, the institutional supports were achieved and arranged for activation of regular oral health education programs, and the prevention plan of metabolic syndrome were needed for changing exercise behavior by conducting suitable exercise programs.

Relationship between Ferric Reducing Antioxidant Power and Metabolic Risk Factors in Korean Women Living in Seoul (서울지역 일부 성인 여성에서 혈청 Ferric Reducing Antioxidant Power와 대사 위험요인간의 상관성에 대한 연구)

  • Kwak, Ho-Kyung;Lee, Mee-Sook;Lim, So-Young;Yoon, Sun
    • Korean Journal of Community Nutrition
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    • v.13 no.1
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    • pp.91-99
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    • 2008
  • The present study was conducted to examine metabolic risk factors and total antioxidant capacity (TAC) of Korean females living in Seoul and to investigate the relationship between the metabolic risk factors and serum TAC. A total of 353 females aged between 20 and 64 participated in the study. Obesity indicators, blood pressure, serum lipid profile and fasting blood glucose were measured as metabolic risk factors. Ferric reducing antioxidant power (FRAP) assay was employed to determine serum TAC of subjects. Obesity indicators such as body mass index, waist circumference and waist-hip ratio were significantly higher in the participants aged $\geq$ 50 y (older group) than in the participants aged 20-49 y (younger group) (p < 0.001). Blood pressure, serum total cholesterol (TC), triglyceride (TG) and fasting blood glucose were also significantly higher in the older group than in the younger group (p < 0.001), demonstrating significant positive correlations between age and MS risk factors. The association between FRAP and MS risk factors were also investigated. FRAP values showed significant positive correlations with age (p = 0.001), serum TG (p = 0.002) and TC (p = 0.03). A tendency of positive association between FRAP and waist circumference was observed without any significant difference (p = 0.06). Increased serum FRAP with central obesity and serum lipids may be interpreted as results of activation of antioxidant defense system against oxidative stress induced by metabolic syndrome (MS) constituent factors. However, to verify the function of FRAP as a potential biomarker of susceptibility to MS various contributors to the plasma antioxidant capacity and their biological relevance related to MS should be elucidated further.

Beneficial effect of Polygoni Multiflori Radix in high fructose diet-induced metabolic syndrome rat model (고과당식이 랫드모델에서 적하수오 투여에 의한 대사증후군 개선효과)

  • Kho, Min Chul;Lee, Yun Jung;Yoon, Jung Joo;Lee, Ho Sub;Kang, Dae Gill
    • The Korea Journal of Herbology
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    • v.30 no.2
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    • pp.11-18
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    • 2015
  • Objectives : Polygoni Multiflori Radix (Jeokhasuo in Korean) is a Oriental traditional herbs widely used in East Asian countries. Overconsumption of fructose results in hypertension, dyslipidemia, obesity and impaired glucose tolerance which have documented as a risk of cardiovascular diseases. This experimental study was designed to investigate the beneficial effects of an ethanol extract from Polygoni Multiflori Radix (PMR) in high-fructose (HF) diet-induced metabolic syndrome rat model. Methods : Sprague-Dawley (SD) rats were divided into three groups; Control group, receiving regular diet and tap water, HF group, and HF + PMR group both receiving supplemented with 65% fructose (n=10), respectively. The HF + PMR group initially received HF diet with PMR (100 mg/kg/day) for 8 weeks. Results : PMR significantly prevented the metabolic disturbances such as hyperlipidemia, hypertension and impaired glucose tolerance. Chronic treatment with PMR significantly decreased body weight, fat weight and adipocyte size, suggesting a role of anti-obesity effect. PMR led to improve the hyperlipidemia through the increase in HDL cholesterol level as well as the decrease in triglyceride and LDL cholesterol level. In addition, PMR suppressed adhesion molecules and endothelin-1 (ET-1) expression in aorta resulting in the decrease of hypertension. In muscle tissue, PMR significantly recovered the HF-induced insulin resistance through increase of insulin receptor substrate-1 (IRS-1), p-$AMPK{\alpha}1/2$, and p-Akt expression. PMR improved HF-induced metabolic disorders and its action was caused by energy metabolism-mediated insulin signaling activation. Conclusions : These results demonstrate that PMR may be a beneficial therapeutic for metabolic syndrome through the improvement of hyperlipidemia, obesity, insulin resistance and hypertension.