Sample records for aminopyrine

  1. Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited. (United States)

    Pijls, Kirsten E; de Vries, Hanne; Nikkessen, Suzan; Bast, Aalt; Wodzig, Will K W H; Koek, Ger H


    As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.

  2. Interactions of Orthosiphon stamineus and Morinda citrifolia with hepatic aminopyrine metabolism by CYP3A in rats

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    J H Chin


    Full Text Available Herb-drug interaction studies have getting attention recently due to the increasingly use of herbal products worldwide. The porpose of the present study was to examine the in vitro effect of methanol leaf extract of Orthosiphon stamineus and Morinda citrofolia fruit juice extract on hepatic aminopyrine metabolism by CYP 3A in different age of normal and STZ-induced diabetic Sprague Dawley (SD rats. Isolated rat hepatocytes were prepared using the collagenase perfusion technique. Aminopyrine was used as a probe substrate to determine the hepatic levels of CYP 3A by measuring the activity of N-demethylation of aminopyrine in rat hepatocytes according to the method described by Nash. Results obtained showed that aminopyrine N-demethylase activity measured from all diabetic rat hepatocytes was not affected by 0. stamineus and M. citrifolia extract. A significant decrease in the aminopyrine N-demethylase activity was observed in the normal old male SD rat hepatocytes preincubated with 0.1 mg/kg (P< 0.01 of methanol extract of 0. stamineus when compared to the respective control group. M. citrifolia juice extract at 0.1 mg/ml (P< 0.01 significantly increased aminopyrine N-demethylase activity in normal adult male SD rat hepatocytes as compared to the control group. For conclusion, both M. citrifolia and 0. stamineus extract could affect the in vitro metabolism of aminopyrine by CYP3A in normal rat hepatocytes. No significant change in the hepatic aminopyrine metabolism was observed in the diabetic rats after incubating with different concentrations of M. citrifolia and 0. stamineus extracts. The observed herb-drug interactions in the present study was age- and disease-dependent.

  3. Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labeled aminopyrine in man

    International Nuclear Information System (INIS)

    Interval sampling of expired breath as a simple, non-invasive assessment of the effect of liver disease upon hepatic microsomal drug metabolism, has been demonstrated with [14C] dimethylaminoantipyrine (aminopyrine). In order to eliminate radiation risk the authors have validated the use of aminopyrine labeled with the stable, non-radioactive isotope 13C. Simultaneous oral administration of both [14C]- and [13C] aminopyrine to five adult subjects without liver disease as well as five patients with known liver disease, resulted in the excretion of label at nearly identical rates in both individual time collections (r=0.94) as well as cumulative excretion for three hours (r=0.97). An oral dose of 2-mg/kg of [13C) aminopyrine resulted in rates of production of 13CO2 significantly greater than baseline variations in 13CO2 production in the fasting, resting subject. Measurements of a single peak value at one half hour correlated closely with the determination of cumulative appearance over three hours (r=0.96). A consistent reproducible increase in the peak production of 13CO2 was observed when five patients received phenobarbital. Stable isotope labeled aminopyrine may be used to detect the effects of disease and treatment upon hepatic N-demethylation activity in human subjects without incurring any risk from radiation. Furthermore, the availability of another isotopic carbon label should make possible the study of direct drug-drug interaction utilizing CO2 analysis. (Auth.)

  4. Assessment of the (14C) aminopyrine breath test in liver disease

    International Nuclear Information System (INIS)

    Different methods of performing the (14C) aminopyrine breath test have been assessed. A tracer dose of 2 μCi without a loading dose and with a single breath collection at two hours was the method selected, since it gave the best discrimination between patients with hepatocellular diseases and normal subjects (5.2 +- 0.2%, mean - SEM). Reduced values occurred in patients with chronic active hepatitis (with and without cirrhosis) (1.5 +- 0.2%), alcoholic cirrhosis (1.7 +- 0.4%) and hepatitis (2.5 +- 0.3%), and late primary biliary cirrhosis suggesting defective microsomal function with respect to demethylation. Normal results were common in early primary biliary cirrhosis. Two weeks of prednisolone therapy caused some improvement in the breath test in nine of ten patients with chronic active hepatitis. It is concluded that the (14C) aminopyrine breath test is a simple test for detecting hepatocellular dysfunction, but has no obvious diagnostic advantage over the determination of serum aspartate transaminase and two hour post-prandial bile-acids. (author)

  5. Early functional recovery for a graft after hepatic transplantation: interest of the aminopyrine-{sup 13}C breath test; Reprise precoce de fonction du greffon apres transplantation hepatique: interet du test respiratoire a l`aminopyrine-{sup 13}C

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    Mion, F.; Queneau, P.E.; Boillot, O.; Minaire, Y.; Delafosse, B. [Hopital Edouard-Herriot, 69 - Lyon (France); Rousseau, M. [Inbiomed, 69 - Lyon (France); Brazier, J.L. [LEACM, 69 - Lyon (France)


    {sup 13}C-aminopyrine breath tests were carried out on 8 patients, just after liver transplantation, in order to examine the recovery of the graft metabolic functions. Test results are compared to usual data from hepatic biology and histology. Quantitative measures on hepatic functional mass are obtained. The relative sensitivity of the test could allow for detection of moderate hepatic dysfunctions. 4 figs., 8 refs.

  6. Experience with the 14C-aminopyrine breath test in hepatic cirrhosis and under the influence of diclofenac-sodium (Voltaren/sup R/)

    International Nuclear Information System (INIS)

    The 14C-aminopyrine breath test is a simple procedure for the non-invasive determination of the microsomal function of the liver. After oral administration of 74 kBq 14C-aminopyrine the 14CO2 activity of the expired breath air is determined in hourly intervals. There is a close correlation between its decrease and the elimination of aminopyrine from the plasma. Both the elimination constant of 14CO2 and the maximal specific 14CO2 activity are useful quantitative parameters of the test. They allow conclusions as to the hepatic demethylation capacity. Both parameters were significantly lower in 15 patients with liver cirrhosis than in 12 control patients. The non-steroidal anti-inflammatory drug diclofenac-sodium did not significantly influence the demethylation of 14C-aminopyrine in 5 patients with rheumatic diseases and in 2 healthy probands. Further experience with the breath test is necessary, especially with respect to its suitability for prospective investigation. (author)

  7. Usefulness of N-dimethyl-13 C-aminopyrine breath test in the diagnosis of liver disease

    International Nuclear Information System (INIS)

    N-dimethyl-13C-aminopyrine breath test was performed in patients with liver disease and healthy controls to compare cumulative 13CO2% dose per 3 hrs expired during breathing. Expired cumulative values were significantly lower in patients with liver cirrhosis than in healthy controls. They were also significantly lower in cirrhosis patients with a history of hepatic insufficiency than in patients without it. However, there was no significant difference between patients with esophageal varices and patients without it. A significant difference was observed between patients with chronic active hepatitis than in healthy controls, but not observed between patients with chronic inactive hepatitis and healthy controls. They did not correlate with sGOT or sGPT, but correlated with prothrombin levels or serum albumin levels. (Namekawa, K.)

  8. Breath analysis of 13CO2 following N-demethylation of 13C-aminopyrine: a measure of liver microsomal function

    International Nuclear Information System (INIS)

    The hepatic microsomal mixed function oxidase enzyme activity has been measured by N-demethylation of 4-dimethyl-14C-aminopyrine (DAP). Analysis of 14CO2 in expired breath has recently been validated in the rat and man as a measure of this function. In the present study we examine the use of DAP labeled with the stable isotope carbon-13, in order to permit broader clinical application of this test by avoiding radiation exposure. Two mg/kg of 86% enriched 13C-DAP were given orally to 4 normal subjects and 5 patients with cholestatic liver disease. All subjects were fasted overnight and studied at rest. Breath samples were collected at 1/2 hour intervals for 3 hours. In all samples the excess of 13CO2 was significantly greater than the variation in baseline after ingestion of unlabeled DAP. In normal subjects the peak production of 13CO2 occurred in the first 1/2 hour sample. Unlabeled DAP (8 mg/kg) clearance from serum correlated with excess 13CO2 production measured in exhaled breath confirming the 14CO2 results. When phenobarbital (180 mg/day) was administered, an increase in exhaled 13CO2 was observed. Measurement of 13CO2 in breath following DAP provides a reproducible clinical measure of microsomal function and drug induction. The use of stable carbon-13 labeled DAP permits measurement of liver microsomal function in patients who cannot receive radioactive labeled DAP

  9. Aminopyrine breath test for evaluation of liver function. How to analyse the 14CO2 data

    International Nuclear Information System (INIS)

    Previous studies in our laboratory have shown that breath analysis of 14CO2, following administration of specifically labelled 14C-dimethylaminoantipyrine, allows assessment of Vsub(max) and Ksub(m) of in vivo demethylation in the rat. Consequently, this procedure was modified for application in man. Whereas in 23 liver normals the disappearance constant ksub(B) of 14CO2 from breath was 21+-SD4%/h, ksub(B) was significantly reduced in 14 patients with alcoholic cirrhosis (8+-4%/h). Breath analysis is suggested as a non-invasive, convenient and valid method for measuring hepatic microsomal demethylation. Breath analysis discriminates between liver normals and patients with impaired liver function as well as established quantitative liver function tests (disappearance rate of BSP, galactose elimination capacity)

  10. Determination of Phenylbutazone and Aminopyrine in Beef by Ultra High Performance Liquid Chromatography-High Resolution Mass Spectrometry%超高效液相色谱-高分辨谱法同时测定牛肉中的苯基丁氮酮和氨基比林

    Institute of Scientific and Technical Information of China (English)

    张海燕; 刘鑫; 严华; 李建辉; 张朝晖; 卢晓宇; 张沫琦; 李岩; 叶晓霞


    建立超高效液相色谱-高分辨质谱法(UPLC-HRMS)同时测定动物源食品中苯基丁氮酮和氨基比林的分析方法.样品前处理使用改进的QuEChERS方法,考察多种溶剂体系,最终选择丙酮和水作为提取溶剂,Acquity UPLCHSS T3色谱柱(150mm×2.1mm,1.8μm)分离,以乙腈和乙酸铵溶液作为流动相进行梯度洗脱,电喷雾正离子(ESr)模式,全扫描模式进行检测.结果表明:苯基丁氮酮在5.0~100.0μg/L范围内线性关系良好(r≥0.995),氨基比林在1.0~100.0μg/L范围内线性关系良好(r≥0.995).牛肉中两种非甾体类阵痛药都有较好的回收率和稳定性:5.0、10.0、20.0μg/kg的添加水平的回收率为76.7%~85.9%,相对标准偏差(RSD,n=6)为5.6%~12.9%.苯基丁氮酮和氨基比林的定量限(RSN=10)分别为5.0μg/kg和1.0μg/kg.该方法简单、快速、灵敏、准确,适合于动物源食品中苯基丁氮酮和氨基比林等非甾体类镇痛剂的快速、高灵敏的分析检测.

  11. Effects of methotrexate on rat P-450 cytochrome mono-oxygenases; Action du methotrexate sur les monooxygenases a cytochromes P-450 chez le rat

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    Guitton, J.; Guilluy, R.; Brazier, J.L. [Faculte de Pharmacie, 69 - Lyon (France); Souillet, G. [Hopital Debrousse, 69 - Lyon (France); Riviere, J.L. [INRA, 69 - Marcy l`Etoile (France); Gerard, F. [Institut Pasteur, 69 - Lyon (France)


    Methotrexate, an anti-cancerous agent, acts as an anti-metabolite of the nucleic acids which synthesis is then inhibited. Using aminopyrine breath test after methotrexate processing, the effects of the molecule on activities of the hepatocyte P-450 cytochrome mono-oxygenases, are studied. Breath micro-tests with carbon 13-labelled aminopyrine have been carried out to observe the metabolism evolution. Micro-test results have been compared to microsomal enzymatic activities for various substrates, and also to P-450 cytochrome ratio. Results show that methotrexate induces a reduction in the P-450 cytochrome ratio, and thus reduce the hepatic biotransformation process. 1 fig., 30 refs.

  12. Effects of methotrexate on rat P-450 cytochrome mono-oxygenases

    International Nuclear Information System (INIS)

    Methotrexate, an anti-cancerous agent, acts as an anti-metabolite of the nucleic acids which synthesis is then inhibited. Using aminopyrine breath test after methotrexate processing, the effects of the molecule on activities of the hepatocyte P-450 cytochrome mono-oxygenases, are studied. Breath micro-tests with carbon 13-labelled aminopyrine have been carried out to observe the metabolism evolution. Micro-test results have been compared to microsomal enzymatic activities for various substrates, and also to P-450 cytochrome ratio. Results show that methotrexate induces a reduction in the P-450 cytochrome ratio, and thus reduce the hepatic biotransformation process. 1 fig., 30 refs

  13. Development of Synthetic Methods of Breath Test Drug Carbon Labeled Methacetin

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Si-qian; CHEN; Bao-jun; LUO; Zhi-fu


    The accurate detection of liver function has important clinical significance.Breath test,due to it’s many advantages such as noninvasive,simple as well as good accuracy when applied to liver function test,has been deeply researched and applied in clinic.There are some common breath tests to reflect hepatocyte microsome function:Aminopyrine breath

  14. The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism. (United States)

    Jakovljevic, V; Raskovic, A; Popovic, M; Sabo, J


    Celery (Apium graveolens) and parsley (Petroselinum sativum), plants used worldwide in human nutrition, are the natural sources of methoxsalen. In this study we investigated the effect of mice pretreatment with juices of this plants on the hypnotic action of pentobarbital and analgesic action of paracetamol and aminopyrine, the drugs involving cytochrome P450 superfamily in their metabolism. In mice pretreated with celery and parsley juices a prolonged action of pentobarbital with respect to control was observed, statistical significance being attained only with parsley-pretreated animals. Both pretreatments increased and prolonged the analgesic action of aminopyrine and paracetamol, pretreatment with parsley being again more effective. Celery and parsley juices given to animals two hours before their decapitation caused a significant decrease of cytochrome P450 in the liver homogenate as compared to control. PMID:12365194

  15. Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo. (United States)

    Veihelmann, A; Brill, T; Blobner, M; Scheller, I; Mayer, B; Prölls, M; Himpel, S; Stadler, J


    Inflammatory stimulation of the liver induces nitric oxide (NO) biosynthesis and suppression of detoxication. In this study the effect of NO biosynthesis on cytochrome P-450 (CYP) enzyme activity was investigated by comparing in vivo and in vitro assays. To establish liver inflammation, CD rats were injected with Corynebacterium parvum (C. parvum) suspension. After 5 days NO biosynthesis was highly induced as indicated by increased NO2- plus NO3- serum concentrations. At the same time the aminopyrine breath test (ABT), measuring CYP activity in vivo, was reduced to 42% and the in vitro assay of aminopyrine turnover was suppressed to 12% of NaCl- injected controls. When C. parvum-injected animals were treated with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), CYP activities significantly improved with an ABT of 76% and an in vitro aminopyrine turnover of 47% of controls. Neither C. parvum injections nor L-NMMA treatment resulted in a significant change of CYP protein concentrations. These data indicate that suppression of xenobiotic metabolism can be attenuated by inhibition of NO biosynthesis during an ongoing process of inflammation. PMID:9277434

  16. Inhibitory effects of beryllium chloride on rat liver microsomal enzymes. (United States)

    Teixeira, C F; Yasaka, W J; Silva, L F; Oshiro, T T; Oga, S


    A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

  17. A study of liver microsomal enzymes in rats following propoxur (Baygon) administration. (United States)

    Nelson, D L; Lamb, D W; Mihail, F


    Groups of rats were given either propoxur, were left as untreated controls, or were given phenobarbital, DDT, chlordane or toxaphene which are known to induce liver microsomal detoxification enzymes. Microsomal enzyme activity was measured by testing the ability of liver homogenates to degrade EPN (O-ethyl O-(4-nitrophenyl) phenylphosphonothioate) to p-nitrophenol. The activity of aminopyrine-N-demethylase, cytochrome P-450 and p-nitroanisole-O-demethylase in liver homogenates of rats receiving propoxur was measured. Liver microsomal detoxification enzymes were not induced by propoxur exposure.


    Institute of Scientific and Technical Information of China (English)

    李赛玲; 朱军


    High fever is referred to that the body temperature exceeds 39℃. Due to aplasia of the cerebral nerve system during infantile stage, continuous high fever may induce temporary functional disturbance of the brain, manifesting as sudden and transient loss of consciousness and local or general muscular spasm that is termed as infantile convulsion. The authors find in clinical practice that sometimes, administration of antipyretics as compound aspirin (APC), compound aminopyrine, etc. has no effect on infantile high fever, if treated with Erjian (MA-H 6) bleeding method, the body temperature may be decreased by 0.5~1.0℃. Here is the report.

  19. Biodegradation of benzidine based dye Direct Blue-6 by Pseudomonas desmolyticum NCIM 2112. (United States)

    Kalme, S D; Parshetti, G K; Jadhav, S U; Govindwar, S P


    Pseudomonas desmolyticum NCIM 2112 was able to degrade a diazo dye Direct Blue-6 (100 mg l(-1)) completely within 72 h of incubation with 88.95% reduction in COD in static anoxic condition. Induction in the activity of oxidative enzymes (LiP, laccase) and tyrosinase while decolorization in the batch culture represents their role in degradation. Dye also induced the activity of aminopyrine N-demethylase, one of the enzyme of mixed function oxidase system. The biodegradation was monitored by UV-Vis, IR spectroscopy and HPLC. The final products, 4-amino naphthalene and amino naphthalene sulfonic acid were characterized by GC-mass spectroscopy.

  20. Lack of in vitro and in vitro effects of fenbendazole on phase I and phase II biotransformation enzymes in rats, mice and chickens. (United States)

    Dalvi, R R; Gawai, K R; Dalvi, P S


    Intraperitoneal administration of 10 mg fenbendazole/kg bw daily for 5 d caused no significant alterations in the activities of hepatic microsomal drug-metabolizing enzymes viz aminopyrine N-demethylase, aniline hydroxylase and cytosolic glutathione S-transferase in rats, mice and chickens. Similarly no significant difference in the amount of microsomal cytochrome P-450 and NADPH-cytochrome c reductase was found between control and treated animals. In vitro incubation of fenbendazole with rat, mouse and chicken microsomes suggests that the drug neither binds to microsomal protein cytochrome P-450 nor inhibits the activities of aminopyrine N-demethylase and aniline hydroxylase. Similarly in vitro addition of fenbendazole to cytosolic glutathione S-transferase from the above species did not alter the activity of this enzyme. The results indicate that fenbendazole does not alter the activity of hepatic microsomal monooxygenase system significantly in rats, mice and chickens at a dosage level of 10 mg/kg body weight. In vitro studies also indicate that fenbendazole does not interact with the hepatic microsomal monooxygenase system, indicating it is not a substrate for cytochrome P-450-dependent monooxygenase system.

  1. Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells

    Institute of Scientific and Technical Information of China (English)

    Hui WANG; Min HUANG; Ren-xiu PENG; Jiang LE


    Aim: To explore the influence and possible mechanism of xenobiotics on adrenal steroidogenesis during fetal development. Methods: Primary human fetal adrenal cortical cells were prepared, cultured and treated with 3-methylcholanthrene, phenobarbital and dexamethasone. The activities of 7-ethoxyresorufin 0-dealkylase, benzphetamine, aminopyrine and erythromycin N-demethylases were measured by enzyme assays. At the same time, quantitative analysis of steroid hormones cortisol, aldosterone, testosterone and progesterone were carried out in cultural medium by radioimmunoassays. Results: The activities of benzphetamine and aminopyrine Ar-demethylase were increased in the cultural fetal adrenal cells treated with phenobarbital (0.25-1 mmol/L) for 24 h. Dexamethasone (25-100 μmol/L) also increased the activity of erythromycin W-demethylase. The activity of 7-ethoxyresorufin 0-dealkylase was undetected in the cells treated without and with 3-methylcholanthrene (0.5-2 μmol/L). Meanwhile, the contents of medium cortisol, aldosterone and progesterone were decreased after treatment with 3-methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the productions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3-methylcholanthrene, phenobarbital or dexamethasone treatment. Conclusion: 3-Methylcholanthrene, phenobarbital or dexamethasone could interfere with the synthesis of cortisol, aldosterone and progesterone in primary human fetal adrenal cortical cells, which likely act through xenobiotic metabolizing-related cytochrome P450 isoform activation.

  2. Enhanced HBsAg synthesis correlates with increased severity of fibrosis in chronic hepatitis B patients.

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    Mei-Zhu Hong

    Full Text Available BACKGROUND AND AIMS: Little is known about whether low serum HBsAg levels result from impaired HBsAg synthesis or a reduced number of hepatocytes caused by advanced liver fibrosis. Therefore, we investigated the capacity for HBsAg synthesis in a cross-sectional cohort of treatment-naïve chronic hepatitis B patients. METHODS: Chronic hepatitis B patients (n = 362 were enrolled; liver biopsies were performed and liver histology was scored, and serum HBsAg and HBV DNA levels were investigated. In the enrolled patients, 183 out of 362 have quantitative serum HBsAg levels. Tissue HBsAg was determined by immunohistochemistry. RESULTS: A positive correlation between serum HBsAg and HBV DNA levels was revealed in HBeAg(+ patients (r = 0.2613, p = 0.0050. In HBeAg(+ patients, serum HBsAg and severity of fibrosis were inversely correlated (p = 0.0094, whereas tissue HBsAg levels correlated positively with the stage of fibrosis (p = 0.0280. After applying the mean aminopyrine breath test as a correction factor, adjusted serum HBsAg showed a strong positive correlation with fibrosis severity in HBeAg(+ patients (r = 0.5655, p<0.0001. The adjusted serum HBsAg values predicted 'moderate to severe' fibrosis with nearly perfect performance in both HBeAg(+ patients (area under the curve: 0.994, 95% CI: 0.983-1.000 and HBeAg(- patients (area under the curve: 1.000, 95% CI: 1.000-1.000. CONCLUSIONS: Although serum HBsAg levels were negatively correlated with fibrosis severity in HBeAg(+ patients, aminopyrine breath test-adjusted serum HBsAg and tissue HBsAg, two indices that are unaffected by the number of residual hepatocytes, were positively correlated with fibrosis severity. Furthermore, adjusted serum HBsAg has an accurate prediction capability.

  3. 丙泊酚对大鼠肝微粒体细胞色素酶P450的影响%Effect of propofol on liver microsomal cytochrome P450 in rats

    Institute of Scientific and Technical Information of China (English)

    李振洲; 陈学新; 陈雅儒; 闫瑞; 孟尽海; 马汉祥; 邓丽琴


    目的:研究丙泊酚对大鼠肝微粒体细胞色素酶P450含量的影响.方法:健康雄性SD大鼠18只,体重180 ~ 220 g,随机分为苯巴比妥钠组、丙泊酚组、生理盐水组,每组6只,分别给予苯巴比妥钠75 mg/kg,丙泊酚3.789 mg/kg及等量生理盐水,持续3 d.测定肝微粒体蛋白和P450的含量以及氨基比林-N脱甲基酶的活性.结果:与生理盐水组比较,苯巴比妥钠组、丙泊酚组肝微粒体蛋白和P450的含量升高;苯巴比妥钠组氨基比林-N脱甲基酶活性明显增高.结论:丙泊酚对大鼠肝微粒体蛋白、细胞色素P450具有诱导作用,对氨基比林-N脱甲基酶的活性无影响.%Objective To explore the effect of propofol on liver microsomal cytochrome P450 in rats.Methods Eighteen male SD rats were randomly assigned to receive phenobarbital of 75 mg/kg (phenobarbital group, n= 6), propofol of 3.789 mg/kg (propofol group, n= 6), or normal saline (control group, n= 6) for three days. Levels of liver microsomal proteins and P450 were detected and activity of aminopyrine N-demethylase was detemined by spectrophotometry. Results As compared with the control group, the levels of microsomal proteins and cytochrome P450 were increased in phenobarbital group and propofol group; the activity of aminopyrine N-demethylase was significantly elevated in phenobarbital group. Conclusions Propofol can induce liver microsomal cytochrome P450 in rats but has no effect on the activity of aminiopyrine N-demethylase.

  4. The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Holst, J J


    Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production in...... and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi.......Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production...... in vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated...

  5. Induction of diphenytriazol on cytochrome CYP1A

    Institute of Scientific and Technical Information of China (English)

    Yun-zhen HU; Tong-wei YAO


    AIM: To study the effects of diphenytriazol on cytochrome P-450 (CYP) enzymes. METHODS: SD rats were pretreated with diphenytriazol. The catalytic activities of rat liver microsomes were determined by assaying ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-dealkylase. Phenacetin and aminopyrine were selected as the substrate of CYP1A and CYP2B, respectively. The concentration of remaining substrate in microsomal incubates was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). The inhibition of fluvoxamine or α-naphthoflavone on phenacetin metabolism was measured. RESULTS: Phenacetin was significantly metabolized in the diphenytriazol-treated microsomes and the metabolic degree increased according to the diphenytriazol-treatment days. There existed a significant correlation between the metabolic degree of phenacetin and EROD in the microsomes pretreated with diphenytriazol. Both fluvoxamine and α-naphthofiavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (Ki) were (5.4± 1.0) μmol/L and (10.4±0.5)μmol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in β-naphthoflavone group, but was significantly different from those in control group and phenobarbital group.CONCLUSION: These results reveal that diphenytriazol is a novel inducer of CYP1A.

  6. High-performance liquid chromatography determination of N- and O-demethylase activities of chemicals in human liver microsomes: application of postcolumn fluorescence derivatization using Nash reagent. (United States)

    Kobayashi, K; Yamamoto, T; Taguchi, M; Chiba, K


    Formaldehyde is liberated in the process of cytochrome P450 (CYP) mediated demethylation of a wide variety of compounds containing the CH(3)N or CH(3)O functionality. A highly sensitive method using a high-performance liquid chromatography (HPLC) system with postcolumn derivatization was developed to measure the liberated formaldehyde as N- and O-demethylase activity of drugs in human liver microsomes. Following the chromatographic separation of formaldehyde on a C18 column, the formaldehyde was reacted with the Nash reagent in the postcolumn reactor at 100 degrees C and detected by the fluorescence method. The results showed that the present method has excellent precision and accuracy. The intra- and interassay variances of this method were less than 10%. The newly developed HPLC method was found to be about 80-fold more sensitive than the colorimetric method in detection of formaldehyde. The N-demethylase activity of sertraline in rat liver microsomes determined by the present method did not differ from those detected by previous methods quantifying produced desmethyl metabolite. The present method has been successfully applied to determine the N-demethylase activities of several drugs, including aminopyrine, erythromycin, fluoxetine, S-mephenytoin, and sertraline, in human liver microsomes. This assay should be useful for generic analysis of N- and O-demethylase activities of xenobiotic and endobiotic chemicals by CYP enzymes. PMID:10964418

  7. Discrimination and quantification of cocaine and adulterants in seized drug samples by infrared spectroscopy and PLSR. (United States)

    Grobério, Tatiane S; Zacca, Jorge J; Botelho, Élvio D; Talhavini, Marcio; Braga, Jez W B


    Middle infrared spectroscopy and multivariate analysis have been applied for the development of methods to perform both quantitative and qualitative analysis of real drug samples seized by the Brazilian Police Federal (BPF). Currently, quantification of cocaine and determination of adulterants in seizures is performed using gas chromatography with flame ionization detection. However, this technique requires a relatively complex sample preparation, higher time of analysis, the destruction of sample and a high cost. In this context, this paper presents a simpler method to quantify cocaine and its major adulterants in seized materials. Out of 375 seizures, taken within a time frame of 2009-2013. A total of 1085 samples were analyzed of which 500 were selected for the calibration set and 585 for the validation set. Cocaine concentration in seized samples was determined by using middle infrared spectroscopy and partial least squares regression (PLSR), obtaining an average prediction error of 3.0% (w/w), precision of 2.0 and 11.8% (w/w) of minimum detectable cocaine concentration in a range varying from 24.2 to 99.9% (w/w). Results indicate that the developed method is able to discriminate between cocaine hydrochloride and free base samples, to quantify cocaine content as well as to estimate the concentration of main adulterants phenacetin, benzocaine, caffeine, lidocaine and aminopyrine. PMID:26448534

  8. Biodegradation of reactive textile dye Red BLI by an isolated bacterium Pseudomonas sp. SUK1. (United States)

    Kalyani, D C; Patil, P S; Jadhav, J P; Govindwar, S P


    A novel bacterial strain capable of decolorizing reactive textile dye Red BLI is isolated from the soil sample collected from contaminated sites of textile industry from Solapur, India. The bacterial isolate was identified as Pseudomonas sp. SUK1 on the basis of 16S rDNA analysis. The Pseudomonas sp. SUK1 decolorized Red BLI (50 mg l(-1)) 99.28% within 1h under static anoxic condition at pH range from 6.5 to 7.0 and 30 degrees C. This strain has ability to decolorize various reactive textile dyes. UV-Vis spectroscopy, FTIR and TLC analysis of samples before and after dye decolorization in culture medium confirmed decolorization of Red BLI. A significant increase in the activities of aminopyrine N-demethylase and NADH-DCIP reductase in cells obtained after decolorization indicates involvement of these enzymes in the decolorization process. Phytotoxicity testing with the seeds of Sorghum vulgare and Phaseolus mungo, showed more sensitivity towards the dye, while the products obtained after dye decolorization does not have any inhibitory effects.

  9. Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    Matthias Ocker; Marion Ganslmayer; Steffen Zopf; Susanne Gahr; Christopher Janson; Eckhart G. Hahn; Christoph Herold


    AIM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF).METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n = 8), interferon/ribavirin (n = 19) or peg-interferon/ribavirin (n = 23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCI) and indocyanine green clearance (ICG)was performed before and 3 mo after initiation of antiviral therapy.RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCV-RNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 mo. Parameters of liver perfusion (SCI and ICG) were not affected by antiviral therapy. In the 14 non-responders,no changes in QTLF values were observed during the treatment period.CONCLUSION: ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antivJral treatment in hepatitis C.

  10. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats. (United States)

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C


    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  11. Effects of frying oil and Houttuynia cordata thunb on xenobiotic-metabolizing enzyme system of rodents

    Institute of Scientific and Technical Information of China (English)

    Ya-Yen Chen; Chiao-Ming Chen; Pi-Yu Chao; Tsan-Ju Chang; Jen-Fang Liu


    AIM: To evaluate the effects of frying oil and Houttuynia cordata Thunb (H. cordata), a vegetable traditionally consumed in Taiwan, on the xenobiotic-metabolizing enzyme system of rodents.METHODS: Forty-eight Sprague-Dawley rats were fed with a diet containing 0%, 2% or 5% H. cordata powder and 15% fresh soybean oil or 24-h oxidized frying oil (OFO)for 28 d respectively. The level of microsomal protein, total cytochrome 450 content (CYP450) and enzyme activities including NADPH reductase, ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-dealkylase (PROD), aniline hydroxylase (ANH), aminopyrine demethylase (AMD), and quinone reductase (QR) were determined. QR represented phase Ⅱ enzymes, the rest of the enzymes tested represented phase Ⅰ enzymes.RESULTS: The oxidized frying oil feeding produced a significant increase in phase Ⅰ and Ⅱ enzyme systems,including the content of CYP450 and microsomal protein,and the activities of NADPH reductase, EROD, PROD, ANH,AMD and QR in rats (P<0.05). In addition, the activities of EROD, ANH and AMD decreased and QR increased after feeding with H. cordata in OFO-fed group (P<0.05). The feeding with 2% H. cordata diet showed the most significant effect.CONCLUSION: The OFO diet induces phases Ⅰ and Ⅱ enzyme activity, and the 2% H. cordata diet resulted in a better regulation of the xenobiotic-metabolizing enzyme system.

  12. Characteristics of VOCs emitted from typical industrial fugitive%典型工业无组织源VOCs排放特征

    Institute of Scientific and Technical Information of China (English)

    王刚; 魏巍; 米同清; 王澎涛; 栾英男; 程水源; 李国昊; 李松


    The pharmaceutical factory, brewery and rubber factory were selected to measure the chemical characteristics of VOCs emissions from their different production processes. The results indicated that in the pharmaceutical factory, VOCs emitted from analgin synthesis and aminopyrine synthesis were mainly composed of benzene, toluene, styrene and other aromatics, and VOCs emitted from acetaminophen synthesis were mainly composed of C4-C6 alkanes. VOCs emitted from brewery and rubber factory were both characterized by toluene, ethylbenzene and p-xylene. Moreover, the maximum incremental reactivity method was applied to analysis the ozone formation potential of VOCs emissions from these factories. The dominant species for ozone formation were benzene, toluene and other aromatics for the analgin synthesis and aminopyrine synthesis in the pharmaceutical factory; c-2-Butene, toluene and isopentane for the acetaminophen synthesis in the pharmaceutical factory; toluene, ethylbenzene and m, p-xylene for the brewery and the rubber factory, respectively. The threshold of diluted multiples was also used to analysis the stench index of these VOCs emissions. The results showed that the odor pollution in the pharmaceutical and brewery was relatively slighter. However, the telescopic device and vulcanizing workshop in the rubber factory were influenced by a certain degree of odor pollution.%选取制药厂、酿酒厂和橡胶厂分析了不同工艺过程 VOCs 排放特征。结果表明,制药厂安乃近合成和氨基比林合成的 VOCs 排放以苯、甲苯和苯乙烯等苯系物为主,乙酰氨基酚合成的VOCs排放主要以C4~C6的烷烃为主,酿酒厂和橡胶厂VOCs排放均以甲苯、乙苯和间,对二甲苯为主。采用最大增量反应活性法对臭氧生成潜势进行分析,制药厂安乃近合成和氨基比林合成 VOCs 单位臭氧生成潜势以苯、甲苯等苯系物为主;乙酰氨基酚合成以顺-2-丁烯、甲苯和异戊烷为主

  13. Inhibition of the gastric H+,K+ -ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews. (United States)

    Schultz, Carla; Bossolani, Myllene P; Torres, Luce M B; Lima-Landman, Maria Teresa R; Lapa, Antonio J; Souccar, Caden


    This work assessed the mechanism underlying the antisecretory gastric acid effect of Plectranthus barbatus Andrews (Lamiaceae) and active constituents. Popularly known as "false-boldo", this plant is used in Brazilian folk medicine to treat gastrointestinal and hepatic ailments. The plant aqueous extract (AE) and isolated compounds were assayed in vivo in pylorus-ligated mice, and in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands and gastric H(+),K(+)-ATPase preparations. Injected into the duodenal lumen, the AE of the plant leaves (0.5 and 1.0 g/kg) decreased the volume (62 and 76%) and total acidity (23 and 50%) of gastric acid secretion in pylorus-ligated mice. Bioguided purification of the AE yielded an active fraction (IC(50)=24 microg/ml) that inhibited acid secretion in rabbit gastric glands with a potency 10 to 18 times greater than that of the originating extract, on both the basal and stimulated acid secretion by histamine (His) (1 microM) or bethanechol (100 microM). At the same concentrations the gastric H(+),K(+)-ATPase activity was also inhibited. The active constituent was chemically identified as the abietanoid dienedione plectrinone A which reduced the H(+),K(+)-ATPase activity with IC(50)=171 microM. The results indicate that inhibition of the gastric proton pump by this diterpenoid may account for the antisecretory acid effect and reputed anti ulcer activity of Plectranthus barbatus. PMID:17166678

  14. Transfer of PCBs via lactation simultaneously induces the expression of P450 isoenzymes and the protooncogenes c-Ha-ras and c-raf in neonates. (United States)

    Borlak, J T; Scott, A; Henderson, C J; Jenke, H J; Wolf, C R


    At the first day of lactation, maternal rats were injected with a single i.p. dose of 100 or 250 mg/kg body weight of a mixture of polychlorinated biphenyls (Aroclor 1254). This treatment caused significant increases in both material and neonatal hepatic cytochrome P-450, cytochrome b5, and cytochrome-c-(P-450) reductase. Transfer of PCBs via lactation resulted in significant increases in hepatic enzyme activities catalysed by neonatal CYP1A1, CYP1A2, CYP2B1, CYP3A1, and CYP2E1 using a variety of substrates. In contrast, the metabolism of dimethylnitrosamine and aminopyrine was only marginally (up to 2-fold) increased in maternal animals four days post treatment. Further measurements showed significant increases in maternal and neonatal epoxide hydrolase, glutathione-S-transferase, and UDP-glucuronyl transferase activities, thus suggesting a coordinated response for an induction of CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1, CYP3A1, and CYP4A1 in both maternal and neonatal CYP2C6, and at the higher dose the expression of neonatal CYP2E1 was significantly reduced. Northern blot analysis provided further evidence for significant increases in maternal and neonatal hepatic CYP1A1, CYP1A2, CYP2B1, and CYP2E1 mRNA, but reduced amounts of CYP2C7 and CYP4A1 mRNA. Additional Northern blot hybridization experiments may suggest an increased expression of the protooncogenes c-Ha-ras and c-raf in the mother and the neonate upon treatment of maternal rats with Aroclor 1254. Lactation itself may result in an increased expression of the latter protooncogenes, but the mRNA of the protooncogenes c-erb A and c-erb B was not detected in any of the tissues examined.

  15. [Formalin-induced minor tremor response as an indicator of pain]. (United States)

    Takahashi, H; Shibata, M; Ohkubo, T; Naruse, S


    Formalin which was said to produce prolonged pain and inflammation was injected subcutaneously into the back of guinea pigs, and minor tremor pain response (MTP-response) was measured using the MT-pick up, integrator and digital volt meter. The MTP-response curve showed a biphasic pattern. Immediately after injection, the MTP-response curve showed a significant peak which lasted for about 2 min (the first phase) and subsequently dipped rapidly, and after 5 min, it began to rise slowly again and had a peak at 30 min (the second phase). Morphine (6 mg/kg, s.c.) inhibited completely the first and second phases. Levallorphan (1.2 mg/kg), however, reversed the inhibitory effect of morphine at the first phase, but not at the second phase. Aspirin (200 mg/kg, i.p.), aminopyrine (100 mg/kg, s.c.) and pentazocine (5 mg-10 mg/kg, s.c.) inhibited significantly the formalin-induced MTP-response at both phases. Pyridinol carbamate (200 mg/kg, i.p.) and hydrocortisone (25 mg/kg, i.p.) had no effect on the MTP-response at the first phase, but inhibited it at the second phase. There was a parallelism between the time course of the vascular permeability induced by formalin and that of the second phase of MTP-response. From these results, it is suggested that the first phase of MTP-response is derived from the direct effect of formalin on free nerve endings, while the second phase is derived from the inflammation. Since two kinds of pain features were differentiated in this method, the relationships with so-called "immediate pain" and "delayed pain" were discussed. Furthermore, this method can be utilized to assess pain and the action of analgesics objectively and quantitatively.

  16. Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Tao-Tao Liu; Ning-Sheng Liang; Yan Li; Fan Yang; Yi Lu; Zi-Qing Meng; Li-Sheng Zhang,


    AIM: To investigate the effects of long-term tea polyphenols (TPs) consumption on hepatic microsomal drug-metabolizing enzymes and liver function in rats.METHODS: TPs were administered intragastrically to rats at the doses of 833 (n=20) and 83.3 (n=20) respectively for six months. Controlled group (n=20)was given same volume of saline solution. Then the contents of cytochrome P450, bS, enzyme activities of aminopyrine N-demethylase (ADM), glutathione S-trasferase (GST) and the biochemical liver function of serum were determined.RESULTS: The contents of cytochrome P450 and b5 in the livers of male rats in high dose groups (respectively 2.66±0.55,10.43±2.78 MS pro-1) were significantly increased compared with the control group (1.08±1.04, 5.51± MS pro-1; P<0.01, respectively). The enzymatic activities of ADM in the livers of female rats in high dose groups (0.91±0.08 mmol@mg MS pro-1min-1) were increased compared with the control group (0.82±0.08 MS pro-1.min-1; P<0.05). The GST activity was unchanged in all treated groups, and the function of liver was not obviously changed.CONCLUSION: The antidotal capability of rats' livers can be significantly improved after long-term consumption of TPs.There are differences in changes of drug-metabolizing enzymes between the sexes induced by TPs and normal condition.

  17. Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate. (United States)

    Hiramatsu, N; Kishida, T; Natake, M


    The effects of dietary pantethine levels on the drug-metabolizing system were investigated under administration of varying amounts of autoxidized linoleate (AL) with rat liver microsomes and S-9 fractions. AL having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (normal), and 125 mg% pantethine (sufficient). The contents and activities of the enzymes in the drug-metabolizing system in the rat liver of each pantethine-level group changed essentially in a similar manner, that is, they were induced at an AL daily dose of 0.2 ml/100 g body weight (i.e., small dose) for 5 successive days and lowered at a daily dose of 0.4 ml/100 g body weight (i.e., large dose) by the same administration period, compared with respective non-AL groups in each of the three pantethine levels. In both non-AL and the small-dose AL, enzyme activities of the electron transfer system in rat liver microsomes, aminopyrine-N-demethylase activity, and metabolic activation of 2-acetylaminofluorene in S-9 fractions were significantly higher in the pantethine-deficient group than in the pantethine-normal and -sufficient groups. In the large-dose AL, the enzyme activities in the drug-metabolizing system decreased significantly in any pantethine levels, though the survival rate of the rats was higher in the pantethine-sufficient group than in the pantethine-normal groups. The results suggest that the pantethine relieves the effect of dosed AL on the drug-metabolizing system in rat liver. PMID:2585150

  18. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    International Nuclear Information System (INIS)

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  19. Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China. (United States)

    Cai, Mei-Quan; Wang, Rong; Feng, Li; Zhang, Li-Qiu


    A simultaneous determination method of 14 multi-class pharmaceuticals using solid-phase extraction (SPE) followed by high-performance liquid chromatography-tandem mass spectrometer (HPLC-MS/MS) was established to measure the occurrence and distribution of these pharmaceuticals in tap water and a drinking water treatment plant (DWTP) in Beijing, China. Target compounds included seven anti-inflammatory drugs, two antibacterial drugs, two lipid regulation drugs, one antiepileptic drug, and one hormone. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 1.80 ng/L and 0.05 to 3.00 ng/L, respectively. Intraday and inter-day precisions, recoveries of different matrices, and matrix effects were also investigated. Of the 14 pharmaceutical compounds selected, nine were identified in tap water of Beijing downtown with the concentration up to 38.24 ng/L (carbamazepine), and the concentration levels of detected pharmaceuticals in tap water (water and finished water at the concentration ranged from 0.10 to 16.23 and 0.13 to 17.17 ng/L, respectively. Five compounds were detected most frequently in DWTP, namely antipyrine, carbamazepine, isopropylantipyrine, aminopyrine, and bezafibrate. Ibuprofen was found to be the highest concentration pharmaceutical during DWTP, up to 53.30 ng/L. DWTP shows a positive effect on the removal of most pharmaceuticals with 81.2-99.5 % removal efficiencies, followed by carbamazepine with 55.4 % removal efficiency, but it has no effect for removing ibuprofen and bezafibrate.

  20. Breath tests: principles, problems, and promise

    International Nuclear Information System (INIS)

    Breath tests rely on the measurement of gases produced in the intestine, absorbed, and expired in the breath. Carbohydrates, such as lactose and sucrose, can be administered in ysiologic doses; if malabsorbed, they will be metabolized to hydrogen by colonic bacteria. Since hydrogen is not produced by human metabolic reactions, a rise in breath hydrogen, as measured by gas chromatography, is evidence of carbohydrate malabsorption. Likewise, a rise in breath hydrogen marks the transit time of nonabsorbable carbohydrates such as lactulose through the small intestine into the colon. Simple end-expiratory interval collection into nonsiliconized vacutainer tubes has made these noninvasive tests quite convenient to perform, but various problems, including changes in stool pH intestinal motility, or metabolic rate, may influence results. Another group of breath tests uses substrates labeled with radioactive or stable isotopes of carbon. Labeled fat substrates such as trioctanoin, tripalmitin, and triolein do not produce the expected rise in labeled breath CO2 if there is fat malabsorption. Bile acid malabsorption and small intestinal bacterial overgrowth can be measured with labeled cholylglycine or cholyltaurine. Labeled drugs such as aminopyrine, methacetin, and phenacetin can be used as an indication of drug metabolism and liver function. Radioactive substrates have been used to trace metabolic pathways and can be measured by scintillation counters. The availability of nonradioactive stable isotopes has made these ideal for use in children and pregnant women, but the cost of substrates and the mass spectrometers to measure them has so far limited their use to research centers. It is hoped that new techniques of processing and measurement will allow further realization of the exciting potential breath analysis has in a growing list of clinical applications

  1. Effects of quinolones on liver microsome cytochrome P450 in rats

    Directory of Open Access Journals (Sweden)

    Yi ZHANG


    Full Text Available Objective  To study and compare the effects of fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and pazufloxacin on the enzyme system of liver microsome cytochrome P450 in rat. Methods  Thirty male Wistar rats were equally assigned into five groups: control group, levofloxacin (LV group, gatifloxacin (GT group, moxifloxacin (MX group and pazufloxacin (PZ group. Each drug was consecutively administered by tail vein injection for 7 days in a dosage of 120 mg/(kg•d. Liver microsomes were prepared by differential centrifugation, the concentration of protein in the liver microsome was measured by Lowry method, the content and activity of cy tochrome P450 were detected by spectrophotometric determination, and the results were analyzed by one-way ANOVA. Results  Compared with control group, the weight of liver in MX group and GT group was significantly reduced (P 0.05. Assay of aminopyrine-N-demethylase activity showed that the difference in enzyme activity was statistically significant between the control group and groups LV, GT and MX (P < 0.01. Erythromycin-N-demethylase activity measurement revealed that the enzyme activity was lowered in GT group and slightly elevated in MX group, and the difference was statistically significant compared with that of control group (P < 0.01. Measurement of activity of rat liver microsomal CYP450 enzyme system subfamily showed that the BROD activity increased in LV, MX and PZ groups (P < 0.01, and slightly decreased in GT group as compared with control group (P < 0.05. The PROD activity increased in GT group, but decreased in PZ group (P < 0.01. The EROD activity increased in all the four groups (P < 0.01. Conclusions  The four fluoroquinolones have some effects on the enzyme system of liver microsome cytochrome P450 in rats, but the effects may be different (enhancement or attenuation of the enzymatic activity depending on the enzymes, and the extent of the decrease of effect is in the

  2. Gene response of CYP360A, CYP314, and GST and whole-organism changes in Daphnia magna exposed to ibuprofen. (United States)

    Wang, Lan; Peng, Ying; Nie, Xiangping; Pan, Benben; Ku, Peijia; Bao, Shuang


    The fate and ecological impact of non-steroidal anti-inflammatory drugs (NSAIDs) in aquatic environments has gained increasingly concern recently. However, limited information is provided about the toxicity mechanism of NSAIDs to aquatic invertebrates. In the present study, we investigated the expression of CYP360A, CYP314, and GST genes involved in the detoxification process and the responses of their associated enzymes activity, as well as whole-organism changes in Daphnia magna exposed to environmentally relevant concentrations of ibuprofen (IBU). Results showed that the total amount of eggs produced per female, total number of brood per female, and body length were significantly decreased under IBU exposure, suggesting the effects of chronic IBU exposure on growth and reproduction of D. magna cannot be ignored. In gene expression level, the CYP360A gene, homologue to CYP3A in mammalian, showed inhibition at low concentration of IBU (0.5μg·L(-1)) and induction at high concentration of IBU (50μg·L(-1)). GST gene also exhibited a similar performance to CYP3A. CYP314 displayed inhibition for short time exposure (6h) and induced with prolonged exposure time (48h) at low concentration of IBU (0.5μg·L(-1)). Erythromycin N-demethylase (ERND) and aminopyrine N-demethylase (APND) related to cytochrome oxidase P450 (CYPs) were inhibited for short time exposure (6h) to IBU and then activated with prolonged exposure time (48h) at low concentration of IBU (0.5μg·L(-1)), while EROD showed a dose-dependent pattern under IBU exposure. As for antioxidative system, induction of glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) was observed in short-term exposure to IBU. Meanwhile, methane dicarboxylic aldehyde (MDA) content increased with the increasing IBU concentration and the delayed exposure time, displaying obvious dose- and time-dependent pattern. In summary, IBU significantly altered some physiological and biochemical parameters and

  3. Modulation of Kupffer cells on hepatic drug metabolism

    Institute of Scientific and Technical Information of China (English)

    Hong Ding; Jing Tong; Shi-Cheng Wu; Deng-Ke Yin; Xian-Fen Yuan; Jian-Yuan Wu; Jun Chen; Gang-Gang Shi


    AIM: To observe the effects of Kupffer cells on hepatic drug metabolic enzymes.METHODS: Kunming mice were ip injected with GdCl310,20, 40 mg/kg to decrease the number and block the function of kupffer cells selectively. The contents of drug metabolic enzymes, cytochrome P450, NADPH-cytochrom C redutase (NADPH-C), aniline hydroxylase (ANH), aminopyrine Ndemethylase (AMD), erythromycin N-demethylase (EMD),and glutathione s-transferase (mGST) in hepatic microsome and S9-GSTpi, S9-GST in supernatant of 9 000 g were accessed 1 d after the injection. The time course of alteration of drug metabolic enzymes was observed on d 1, 3, and 6 treated with a single dose GdCl3. Mice were treated with Angelica sinensis polysaccharides (ASP) of 30, 60, 120 mg/kg, ig, qd ×6 d, respectively and the same assays were performed.RESULTS: P450 content and NADPH-C, ANH, AMD, and END activities were obviously reduced 1 d after Kupffer cell blockade. However, mGST and S9-GST activities were significantly increased. But no relationship was observed between GdCl3 dosage and enzyme activities. With single dose GdCl3 treatment, P450 content, NADPH-C, and ANH activities were further decreased following Kupffer cell blockade lasted for 6 d, by 35.7%, 50.3%, 36.5% after 3 d, and 57.9%, 57.9%, 63.2% after 6 d, respectively. On the contrary, AMD, EMD, mGST, and Sg-GST activities were raised by 36.5%, 71.9%, 23.1%, 35.7% after 3 d,and 155%, 182%, 21.5%, 33.7% after 6 d, respectively.Furthermore, the activities of drug metabolic enzymes were markedly increased after 30 mg/kg ASP treatment,and decreased significantly after 120 mg/kg ASP treatment.No change in activity of Sg-GSTpi was observed in the present study.CONCLUSION: Kupffer cells play an important role in the modulation of drug metabolic enzymes. The changes of drug metabolic enzyme activities depend on the time of kupffer cell blockade and on the degree of Kupffer cells activated. A low concentration of ASP increases the activities of drug

  4. Liquid Chromatogram and Mass-spectrography for Rapid Determination of Illegally Added Amidopyrine in Pediatric Qingjie Particles%液相色谱-质谱法快速测定小儿清解颗粒中非法添加的氨基比林

    Institute of Scientific and Technical Information of China (English)



    OBJECTIVE:To establish a rapid accurate identification method of illegally added amidopyrine in pediatric Qingjie particles .METHODS:Illegally added acetanilide detumescence chemical drug amidopyrine from four different companies were screened by liquid chromatogram ( LC ) and mass-spectrography ( MS ) , and reference substance of secondary mass spectra were compared .RESULTS: In the sample mass spectrum , there were three samples were not consistent with the reference substance of primary and secondary mass spectrum peak , and a manufacturer of sample pattern was consistent with the reference substance of primary and secondary mass spectrum peak.CONCLUSIONS: Application of LC and MS method can accurately identify whether Chinese medicine preparations contains illegal added amidopyrine , and the content of aminopyrine can be calculated accurately .%目的:建立快速准确鉴定小儿清解颗粒中非法添加氨基比林的方法。方法:用液相色谱质谱联用技术对4种不同厂家小儿清解颗粒中非法添加消肿止痛类化学药品氨基比林进行筛查,与氨基比林对照品的一、二级质谱图进行比较。结果:在样品质谱图中有3家样品的图谱与对照品有不一致的一级质谱峰与二级质谱峰,1个厂家的样品图谱有与对照品有一致的一级质谱峰与二级质谱峰。结论:应用液相色谱-质谱法可快速准确鉴定出中药制剂中是否含有非法添加的氨基比林,并可以准确计算添加氨基比林的含量。

  5. Hepatic calcium efflux during cytochrome P-450-dependent drug oxidations at the endoplasmic reticulum in intact liver. (United States)

    Sies, H; Graf, P; Estrela, J M


    During metabolism of (type I) drugs by cytochrome P-450-dependent monooxygenase of the endoplasmic reticulum, the NADPH/NADP+ ratio in rat liver selectively decreases to approximately one-half of the control values, whereas the NADH/NAD+ ratio remains practically unaffected [Sies, H. & Brauser, B. (1970) Eur. J. Biochem. 15, 521-540]. In view of the observations with isolated mitochondria [Lehninger, A. L., Vercesi, A. & Bababunmi, E. A. (1978) Proc. Natl. Acad. Sci. USA 75, 1690-1694] of stimulated Ca2+ efflux upon nicotinamide nucleotide oxidation, the selective oxidation of NADPH in cytosol and mitochondria during drug oxidations was considered a useful experimental tool for the determination of whether the oxidation of NADPH or of NADH is responsible for Ca2+ efflux. With perfused livers from phenobarbital-treated rats, Ca2+ efflux was demonstrated, amounting to 8 nmol/min per gram of liver (wet weight), with aminopyrine, ethylmorphine, or hexobarbital as drug substrates. Drug-associated Ca2+ release was diminished when the inhibitor metyrapone was also present, or when drug oxidation was suppressed during N2 anoxia or in the presence of antimycin A in livers from fasted rats. Ca2+ efflux was elicited also by infusion of the thiol oxidant diamide, and by t-butyl hydroperoxide. However whereas Ca2+ efflux elicited by these compounds was restricted upon addition of the thiol dithioerythritol, there was little, if any, sensitivity of the drug-associated Ca2+ efflux to the thiol. Further mitochondrial oxidation of NADPH by addition of ammonium chloride had no effect on drug-associated Ca2+ efflux. Prior addition of the alpha-agonist phenylephrine suppressed the Ca2+ release by drug addition. While the molecular mechanism involved in Ca2+ efflux from liver mitochondria and from hepatocytes as well as the regulatory significance are not yet known, it is concluded from the present experiments that in case of nicotinamide nucleotide-linked Ca2+ efflux the oxidation of

  6. Concurrent subacute exposure to arsenic through drinking water and malathion via diet in male rats: effects on hepatic drug-metabolizing enzymes

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    Naraharisetti, Suresh Babu [Indian Veterinary Research Institute, Division of Pharmacology and Toxicology, Izatnagar, Uttar Pradesh (India); University of Washington, Department of Medicinal Chemistry, Seattle, WA (United States); Aggarwal, Manoj [Indian Veterinary Research Institute, Division of Pharmacology and Toxicology, Izatnagar, Uttar Pradesh (India); Institut fuer Arbeitsphysiologie an der Universitaet Dortmund, Dortmund (Germany); Sarkar, S.N.; Malik, J.K. [Indian Veterinary Research Institute, Division of Pharmacology and Toxicology, Izatnagar, Uttar Pradesh (India)


    Arsenic is a known global groundwater contaminant, while malathion is one of the most widely used pesticides in agriculture and public health practices in the world. Here, we investigated whether repeated exposure to arsenic at the groundwater contamination levels and to malathion at sublethal levels exerts adverse effects on the hepatic drug-metabolizing system in rats, and whether concurrent exposure is more hazardous than the single agent. Male Wistar rats were exposed daily to 4 or 40 ppm of arsenic via drinking water, 50 or 500 ppm of malathion-mixed feed and in a similar fashion co-exposed to 4 ppm of arsenic and 50 ppm of malathion or 40 ppm of arsenic and 500 ppm of malathion for 28 days. At term, toxicity was assessed by evaluating changes in body weight, liver weight, levels of cytochrome P{sub 450} (CYP), cytochrome b{sub 5} and microsomal and cytosolic proteins, and activities of aminopyrine-N-demethylase (ANDM), aniline-P-hydroxylase (APH), glutathione-S-transferase (GST) and uridine diphosphate glucuronosyltransferase (UGT) in liver. Arsenic and malathion alone did not alter body weight and liver weight, but these were significantly decreased in both the co-exposed groups. These treatments decreased the activities of ANDM and APH and the levels of liver microsomal and cytosolic proteins, increased GST activity and had no effect on UGT activity. The effects of exposure to low-dose and high-dose combinations on the activities of either phase I or phase II drug-metabolizing enzymes and protein content were mostly similar to that produced by the respective low and high dose of either arsenic or malathion, except APH activity. The effect of arsenic (40 ppm) on APH activity was partially, but significantly, inhibited by malathion (500 ppm). Results indicate that the body or liver weights and the biochemical parameters were differentially affected in male rats following concurrent subacute exposure to arsenic and malathion, with the co-exposure appearing

  7. Effects of orally applied butyrate bolus on histone acetylation and cytochrome P450 enzyme activity in the liver of chicken – a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Mátis Gábor


    Full Text Available Abstract Background Butyrate is known as histone deacetylase inhibitor, inducing histone hyperacetylation in vitro and playing a predominant role in the epigenetic regulation of gene expression and cell function. We hypothesized that butyrate, endogenously produced by intestinal microbial fermentation or applied as a nutritional supplement, might cause similar in vivo modifications in the chromatin structure of the hepatocytes, influencing the expression of certain genes and therefore modifying the activity of hepatic microsomal drug-metabolizing cytochrome P450 (CYP enzymes. Methods An animal study was carried out in chicken as a model to investigate the molecular mechanisms of butyrate’s epigenetic actions in the liver. Broiler chicks in the early post-hatch period were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day for five days. After slaughtering, cell nucleus and microsomal fractions were separated by differential centrifugation from the livers. Histones were isolated from cell nuclei and acetylation of hepatic core histones was screened by western blotting. The activity of CYP2H and CYP3A37, enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions. Results Orally added butyrate, applied in bolus, had a remarkable impact on nucleosome structure of hepatocytes: independently of the dose, butyrate caused hyperacetylation of histone H2A, but no changes were monitored in the acetylation state of H2B. Intensive hyperacetylation of H3 was induced by the higher administered dose, while the lower dose tended to increase acetylation ratio of H4. In spite of the observed modification in histone acetylation, no significant changes were observed in the hepatic microsomal CYP2H and CYP3A37 activity. Conclusion Orally added butyrate in bolus

  8. Captan impairs CYP-catalyzed drug metabolism in the mouse. (United States)

    Paolini, M; Barillari, J; Trespidi, S; Valgimigli, L; Pedulli, G F; Cantelli-Forti, G


    To investigate whether the fungicide captan impairs CYP-catalyzed drug metabolism in murine liver, kidney and lung, the modulation of the regio- and stereo-selective hydroxylation of testosterone, including 6beta-(CYP3A), 6alpha-(CYP2A1 and CYP2B1) and 16alpha-(CYP2B9) oxidations was studied. Specific substrates as probes for different CYP isoforms such as p-nitrophenol (CYP2E1), pentoxyresorufin (CYP2B1), ethoxyresorufin (CYP1A1), aminopyrine (CYP3A), phenacetin and methoxyresorufin (CYP1A2), and ethoxycoumarin (mixed) were also considered. Daily doses of captan (7.5 or 15 mg/kg b.w., i.p.) were administered to different groups of Swiss Albino CD1 mice of both sexes for 1 or 3 consecutive days. While a single dose of this fungicide did not affect CYP-machinery, repeated treatment significantly impaired the microsomal metabolism; in the liver, for example, a general inactivating effect was observed, with the sole exception of testosterone 2alpha-hydroxylase activity which was induced up to 8.6-fold in males. In vitro studies showed that the mechanism-based inhibition was related to captan metabolites rather than the parental compound. In the kidney, both CYP3A- and CYP1A2-linked monooxygenases were significantly induced (2-fold) by this pesticide. Accelerated phenacetin and methoxyresorufin metabolism (CYP1A2) was also observed in the lung. Data on CYP3A (kidney) and CYP1A2 (kidney and lung) induction were corroborated by Western immunoblotting using rabbit polyclonal anti-CYP3A1/2 and CYP1A1/2 antibodies. By means of electron spin resonance (EPR) spectrometry coupled to a spin-trapping technique, it was found that the recorded induction generates a large amounts of the anion radical superoxide (O*2-) either in kidney or lung microsomes. These findings suggest that alterations in CYP-associated activities by captan exposure may result in impaired (endogenous) metabolism as well as of coadministered drugs with significant implications for their disposition. The

  9. Gene response of CYP360A, CYP314, and GST and whole-organism changes in Daphnia magna exposed to ibuprofen. (United States)

    Wang, Lan; Peng, Ying; Nie, Xiangping; Pan, Benben; Ku, Peijia; Bao, Shuang


    The fate and ecological impact of non-steroidal anti-inflammatory drugs (NSAIDs) in aquatic environments has gained increasingly concern recently. However, limited information is provided about the toxicity mechanism of NSAIDs to aquatic invertebrates. In the present study, we investigated the expression of CYP360A, CYP314, and GST genes involved in the detoxification process and the responses of their associated enzymes activity, as well as whole-organism changes in Daphnia magna exposed to environmentally relevant concentrations of ibuprofen (IBU). Results showed that the total amount of eggs produced per female, total number of brood per female, and body length were significantly decreased under IBU exposure, suggesting the effects of chronic IBU exposure on growth and reproduction of D. magna cannot be ignored. In gene expression level, the CYP360A gene, homologue to CYP3A in mammalian, showed inhibition at low concentration of IBU (0.5μg·L(-1)) and induction at high concentration of IBU (50μg·L(-1)). GST gene also exhibited a similar performance to CYP3A. CYP314 displayed inhibition for short time exposure (6h) and induced with prolonged exposure time (48h) at low concentration of IBU (0.5μg·L(-1)). Erythromycin N-demethylase (ERND) and aminopyrine N-demethylase (APND) related to cytochrome oxidase P450 (CYPs) were inhibited for short time exposure (6h) to IBU and then activated with prolonged exposure time (48h) at low concentration of IBU (0.5μg·L(-1)), while EROD showed a dose-dependent pattern under IBU exposure. As for antioxidative system, induction of glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) was observed in short-term exposure to IBU. Meanwhile, methane dicarboxylic aldehyde (MDA) content increased with the increasing IBU concentration and the delayed exposure time, displaying obvious dose- and time-dependent pattern. In summary, IBU significantly altered some physiological and biochemical parameters and

  10. Antinociceptive, anti-inflammatory and diuretic properties of Polygonum barbatum (L. Hara var. barbata Propriedades antinociceptiva, antiinflamatória e diurética dos extratos de P. barbatum (L. Hara var. barbata

    Directory of Open Access Journals (Sweden)

    M. Abdul Mazid


    Full Text Available The antinociceptive, anti-inflammatory and diuretic properties of the extracts of P. barbatum (L. Hara var. barbata, Polygonaceae, at the doses of 200 and 400 mg/kg body weight, were evaluated in mice/rat models using, respectively, the acetic-acid-induced writhing method, the carrageenan-induced edema test and the Lipschitz method. In the acetic-acid-induced writhing test in mice, all extracts displayed a dose dependent analgesic effect. The most potent analgesic activity was observed with the petroleum ether extract at the dose of 400 mg/kg body weight with an inhibition of writhing response 46.8% compared to 62.2% for the positive control aminopyrine. Petroleum ether extract at the dose of 400 mg/kg body weight also displayed the highest levels of anti-inflammatory activity after 2 h with the 39.3% inhibition of paw edema, and this effect was better than the effect observed by the conventional anti-inflammatory agent phenylbutazone (maximum inhibition of 38.3% after 4 h. All extracts increased urine volume in a dose-dependent manner, and the ethyl acetate extract showed a significant level of diuresis comparable to that of the standard diuretic agent furosemide.As propriedades antinociceptiva, antiinflamatória e diurética dos extratos de P. barbatum (L. Hara var. barbata, Polygonaceae, nas doses de 200 e 400 mg/kg de peso corpóreo foram avaliadas em modelos utilizando camundongos/ratos, respectivamente, o método de contorções induzidas por ácido acético, o teste de edema induzido por carragenina e o método de Lipschitz. No método de contorções induzidas por ácido acetic, todos os extratos apresentaram efeito nociceptivo dose dependente. O efeito nociceptivo mais potente foi observado com o extrato de éter de petróleo na dose de 400 mg/kg com uma inibição das contorções de 46,8% comparado com o controle positivo de aminopirina de 62,2%. O extrato de éter de petróleo na dose de 400 mg/kg também mostrou maior atividade

  11. Simultaneous Determination of Thirteen Chemical Materials Illegally Added in Antirheumatic Health Products by HPLC-DAD%HPLC-DAD法同时测定抗风湿类保健食品中非法添加的13种化学成分

    Institute of Scientific and Technical Information of China (English)



    Objective: To simultaneously detect 13 anti-rheumatic chemical components added illegally in health food. Methods: Using HPLC-DAD, the separation was performed on the XBridge C18 (4.6 mm×250 mm, 5μm) column by gradient elution at a flow rate of 1.0 mL·min-1. The mobile phase consisted of ace-tonitril-0.02 mol·L-1 ammonium acetate (including 0.075% acetic acid) and the detection wavelength was 230 nm. Results: The correlation coefficients of the equation of linear regression were above 0.9999. The average recoveries were 95.6%-102.5% and the relative standard deviations were less than 1.6% (n=3). U-PLC-QTOF-MS was used to further confirm. Conclusion: The method is simple and reliable, and can be used for simultaneously detecting 13 anti-rheumatic chemical components (acetaminophen, aspirin, trimetho-prim, aminopyrine, hydrocortisone, piroxicam, dexamethasone, naproxen, prednisone acetate, diclofenac sodi-um, indometacin, phenylbutazone and ibuprofen) in health food.%目的:同时检测抗风湿类保健食品中非法添加的13种化学成分。方法:采用高效液相色谱串联二极管阵列检测器法,使用XBridge C18(4.6 mm×250 mm,5μm)色谱柱进行分离,流动相为乙腈-0.02 mol·L-1醋酸铵(含0.075%乙酸),梯度洗脱,流速为1.0 mL·min-1,检测波长为230 nm。结果:各化学成分线性回归方程的相关系数均大于0.9999,平均回收率为95.6%~102.5%, RSD均小于1.6%(n=3),并用UPLC-QTOF-MS法进一步确证。结论:该方法操作简便可靠,能同时测定抗风湿类保健食品中非法添加的13种化学成分,分别为对乙酰氨基酚、阿司匹林、甲氧苄啶、氨基比林、氢化可的松、吡罗昔康、地塞米松、萘普生、醋酸泼尼松、双氯芬酸钠、吲哚美辛、保泰松、布洛芬。

  12. Effects of Ibuprofen on the phase I metabolic enzymes and antioxidant defence system of the Yellow Catfish (Pelteobagrus fulvidraco)%布洛芬对黄颡鱼Ⅰ相代谢酶及其抗氧化系统的影响

    Institute of Scientific and Technical Information of China (English)

    武小燕; 彭颖; 廖伟; 李义刚; 苏甜; 欧瑞康; 陈昆慈; 李凯彬; 聂湘平


    The toxic effects of ibuprofen in environmental levels of 0. 05 , 0.5, 5 and 50 μg · L-1 via waterborne exposure on the phase I metabolic enzymes and antioxidant defence system of the yellow catfish were investigated. The activities of aminopyrine N-demethylase ( APND) , erythromycin N-demethylase (ERND) , 7-ethoxyresorufin -O-deethylase (EROD) and glutathione-S-transferase (GST) enzymes were induced at the initial stages and gradually inhibited with the extension of exposure time. After 24 h exposure, the highest levels of APND and ERND were detected at the concentration of 5 μg·L-1. Obvious EROD induction was observed at 24 h in all IBU exposure groups compared to the control except 0. 05 μg· L-1 group and then returned to the normal level after 168 h. The highest value occurred at 24 h for GST and at 168 h for catalase (CAT). The content of malondialdehyde (MDA) decreased significantly after 24 h exposure and reached the highest value at 72 h. ERND was a sensitive parameters and may be used as a potential biomarker for IBU exposure.%使用环境相关浓度水平(0.05、0.5、5、50 μg· L-1)的布洛芬(Ibuprofen,IBU)对黄颡鱼进行水体暴露,研究IBU对黄颡鱼Ⅰ相代谢酶及其抗氧化系统的影响.结果表明,随着暴露时间的延长,IBU对黄颡鱼肝脏Ⅰ相代谢P450酶系的氨基比林-N-脱甲基酶(APND)、红霉素-N-脱甲基酶(ERND)、7-乙氧基-异吩噁唑酮-脱乙基酶(EROD)和Ⅱ相代谢谷胱甘肽硫转移酶(GST)均表现出先诱导后抑制的作用.暴露24 h时,IBU浓度为5 μg· L-1实验组对Ⅰ相代谢酶APND和ERND的诱导程度最大.当暴露时间达到168 h时,0.5 μg·L-1浓度组中APND和ERND活性均受到极显著抑制.Ⅰ相代谢酶EROD活性在暴露24 h后,除0.05 μg· L-1浓度组无明显变化外,其它浓度组皆受到显著诱导,随着暴露时间延长到168 h时,逐渐恢复到初始水平.GST活性在暴露24 h后,除0.05 μg·L-1浓度组外,其它浓度组均受到最大

  13. 异育银鲫各组织器官中细胞色素P450药酶活性的比较%Comparative Activity of microsomal cytochrome P450 in various tissues and organs in allogynogenesis silver crucian carp Carassius auratus gibelio

    Institute of Scientific and Technical Information of China (English)

    贾娴; 胡琳琳; 房文红; 汪开毓; 胡晓


    The activities and tissue distribution of cytochrome P450 drug - metabolizing enzyme were studied in liver, kidney, gill and muscle of allogynogenesis silver crucian carp Carassius auratus gibelio. Microsomal P450 and b5 contents were determined by the method of CO differential spectroscopy in liver,kidney,gill,intestine and muscle microsomes. Both cytochrome P450 and cytocorome b5 contents were found to be the maximum in liver microsome, and the minimum in muscle microsome. The activities of CYP2B, CYP3A and CYP2E were evaluated by microsomal N - demethylation of aminopyrine ( APD), erythromycin (ERND) and 4 - aniline - hydroxylation (AH) as probe specific reactions. The activities of APD ( 1. 668 ± 0. 104) and ERND (0.941 ± 0. 061 ) nmol/( min · mg)were the maximum in liver microsome, and the minimum in muscle microsome [ (0.245 ± 0.011 ), and (0. 078 ± 0.019) nmol/( min · mg)]. The maximal AH activity (0. 052 ± 0. 009)nmol/( min · mg) was observed in liver microsome, but not be detected in muscle microsome, indicating that the above -mentioned cytochrome P450 isoenzymes were available in main tissue microsoms in the crucian carp, and the APD, ERND and AH activities were different in different tissues, the maximal activities being observed in liver microsome.%对异育银鲫Carassius auratus gibelio肝胰脏、肾、鳃、肠和肌肉等组织器官中细胞色素P450(CYP450)主要药酶活性进行检测,研究其在异育银鲫各组织中的分布.结果显示:以CO还原差示光谱法测得异育银鲫肝胰脏、肾、鳃、肠、肌肉微拉体的细胞色素P450及b5含量均以肝胰脏微粒体中最高,其次为肾、鳃、肠微粒体,肌肉中最低.以氨基比林N-脱甲基、红霉素N-脱甲基、苯胺-4-羟化反应分别作为CYP2B、CYP3A和CYP2E的探针反应,测得氨基比林N-脱甲基酶(APD)及红霉素N-脱甲基酶(ERND)活性在上述组织中分布差异性类似,均表现为肝胰脏微粒体中最高,分别为(1.668±0

  14. 氟甲喹对异育银鲫细胞色素CYP450主要药酶的影响%Effects of flumequine on cytochrome P450 enzymes in allogynogenetic silver crucian carp,Carassius auratus gibelio

    Institute of Scientific and Technical Information of China (English)

    胡晓; 房文红; 汪开毓; 孙贝贝; 胡琳琳; 周帅; 周俊芳


    activity(P<0.01). However, the other P450 monooxygenases, such as erythromycin N-demethylase (ERND) [177.98 pmol/(mg.min)], aminopyrine N-demethylase [934.40 pmol/(mg.min)] and ethoxycoumarin O-deethylase (ECOD) [9.84pmol/ (mg.min)]were not significantly affected by flumequine, comparing with these activities in control [140.90 pmol/(mg·min), 850.71 pmol/(mg.min) and 8.93 pmol/(mg.min)], respectively. Except that the ERND activity in kidney tissue was higher than that in liver, the activities ofAPD, EROD and ECOD were the highest in liver tissue. An immunoblot analysis with rabbit anti-rat P4501A polyclonal antibody showed that CYP 1A protein expression in flumequine-treated carps was markedly higher than that in control carps, which was consistent with the trend in EROD activities. These findings suggest that P450 lA isoform, constitutively expressed in crucian carp, was particularly susceptible to activation by flumequine. Semiquantitative RT-PCR indicated that CYP 1A mRNA was not affected by flumequine. In vitro assay, microsomes incubating with various concentrations of flumequine demonstrated that this fluoroquinolone antibiotic had no induction or inhibition of CYP1A. On the basis of the above, liver CYP 1A induction of flumequine on carp occurs at the post-translation level, which may enhance protein stability.


    Institute of Scientific and Technical Information of China (English)

    周建伟; 李季; 李宁; 张凡; 胡玲香; 赵菁菁; 张颜; 王成伟


    Objective To discuss the difference of electro-acupuncture and drug in controlling the attack of migraine due to hyperactivity of liver yang.Methods Three-centered random control method was used,and 300 qualified cases were randomly divided into treatment group(146 cases according to the design)and control group(140 cases),which were respectively treated with eIectro-acupuncture and drugs(Compound Aminopyrine Phenacetin Tablets,Ergotamine Caffeine Tablets,Diazepam Tablets),and observed the overall effect and scores of headache,accompanying symptoms,psychological and social adaptability scores,life quality scores,TCM symptoms scores and follow-up results before and after the treatment.Results In treatment group,the successful rate of attack control was 47.3%,the improvement rate was 73.3%,and the total effectiveness was 90.4%,the clinical control rate and improvement were much superior to control group(the clinical controI rate 35.7%,improvement 61.4%,the totaI effectiveness 85.7%),P<0.01,the difference in effect was mainly reflected in patients with moderate severity;the total scores of TCM syndrome after the treatment was obviously significant or very obviously significant(P<0.05,P<0.01),but the headache scores between two groups was not obviously significant(P>0.05),the difference in accompanying symptoms was significant(P<0.01);the long term attack control action in two groups was not satisfactory,the recurrence was similar(P>0.05),the severity of headache in recurrence cases of treatment group was alleviated and superior to control group(P<0.01),the occurrence of headache after the treatment is much less than that before the treatment and the situation after 2 months was superior to controI group(P<0.01).Sleepiness and redness of face in some patients which were seen in control group weren't seen in treatment group.Conclusion Electro-acupuncture on Tàiyáng(太阳EX-HN5)can control the attack of migraine due to hyperactivity of liver yang

  16. 臭牡丹根提取物对小鼠的镇痛效应%Analgesic effect of extract of clerodendron bungei steud roots in mice

    Institute of Scientific and Technical Information of China (English)

    刘建新; 谢水祥; 周俐; 连其深


    BACKGROUND: Clerodendron bungei steud(CBS) is a tree from genera of Verbena L. In the present pharmacological studies, CBS has showed anti-inflammatory, antineoplasic, nonspecific immunity-enhancing effects. Myoelectric effect of stimulating uterus round ligament is related with agitating adrenergic α receptor. The experiments about analgesic effect are few.OBJECTIVE: To observe the antinociceptive effect of ethanol extract of CBS in mice through hot plate and writhing tests.DESIGN: Randomized controlled experiment with animals as subjects.SETTING: Departmcent of Pharmmacology, Gannan Medical College.MATERIALS: The experiment was performed in Department of Pharmacology, Gannan Medical College from March to June 2004. A total of 120Kunming white mice, weighing(20 ± 2) g were provided by the Experiment Animal Center of Gannan Medical College.INTERVENTIONS: In the writhing test, 50 mice were randomly divided into normal saline, aminopyrine group(0. 1 g/kg), morphine group(0.01 g/kg)and extract of CBS groups(20 g/kg, 40 g/kg) . There were 10 mice in each group. Forty minutes after intraperitoneal injection. 6 mL/L acetic acid (10 mL/kg) was injected intraperitoneally, 5 minutes later, the number of writhing body and inhibitory rate of writhing body were observed for 10minutes. In hot plate test, 40 mice were randomly divided into normal saline group, morphine group(0.01 g/kg) and extract of CBS groups(20 g/kg,40 g/kg). There were 10 mice in each group. After intraperitoneal injection,the mice were put on the hot plate, and the temperature was(55 ±0.5) C. The pain threshold was recorded 15, 30 and 60 minutes after administration. And 30 white mice were randomly divided into naloxone 0. 04 g/kg + morphine 0.01 g/kg group, aloxone 0.04 g/kg + extract of CBS 40 g/kg group,naloxone 0.04 g/kg + normal saline group for hot plate test antagonized by naloxone(40 mg/kg) . The mice were injected intraperitoneally. The duration of pain reaction were recorded 15, 30, 60 and 90