WorldWideScience

Sample records for aminopyrine

  1. Kinetics and metabolism of pyrazolones (propyphenazone, aminopyrine and dipyrone)

    Science.gov (United States)

    Volz, Manfred; Kellner, Hans-Martin

    1980-01-01

    1 Propyphenazone 220 mg was administered orally to volunteers. Maximum plasma concentrations between 1.5 μg/ml and 3.5 μg/ml were found 30 min later. After comparable doses plasma concentrations in dog and rabbit were lower. The distribution volumes were 2 1/kg. 2 The major metabolic route of propyphenazone is demethylation. The main urinary metabolite is the enolglucuronide of N-(2)-demethylprophyphenazone. 3 Aminopyrine is rapidly and almost completely absorbed after oral administration. Maximum plasma concentrations of 10 μg/ml are reached 1.5 h after a 500 mg dose. The biological half-life is 2-3 h, the relative distribution volume 60% on average, and binding to plasma proteins approximately 15%. 4 Unchanged aminopyrine is only excreted in small quantities. The major routes of metabolism are demethylation (4-methylaminoantipyrine and 4-aminoantipyrine) and acylation (4-acetyl and 4-formylaminoantipyrine). There are other biotransformation products. 5 After oral administration of [14C]-dipyrone 480 mg the maximum serum concentration of 13.4±0.8 μg/ml occurred at 1-1.5 hours. 6 Dipyrone was not detectable in serum or urine. Four of seven metabolites were identified, and were identical with the main metabolites of aminopyrine. PMID:7002187

  2. Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells

    International Nuclear Information System (INIS)

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. [14C]Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated [14C]aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on [14C]aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased [14C]aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion

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

    Directory of Open Access Journals (Sweden)

    J H Chin

    2009-01-01

    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.

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

    OpenAIRE

    J H Chin; M Mahfoudh; H H Abas

    2009-01-01

    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 ...

  5. Effect of adenosine and adenosine analogs on ( sup 14 C)aminopyrine accumulation by rabbit parietal cells

    Energy Technology Data Exchange (ETDEWEB)

    Ota, S.; Hiraishi, H.; Terano, A.; Mutoh, H.; Kurachi, Y.; Shimada, T.; Ivey, K.J.; Sugimoto, T. (Univ. of Tokyo (Japan))

    1989-12-01

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on (14C)aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. (14C)Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated (14C)aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on (14C)aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased (14C)aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

  6. 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.)

  7. Inhibition by Vitamin E of Cholangiocarcinoma Induction due to Combined Nitrite and Aminopyrine.

    Science.gov (United States)

    Thamavit, Witaya; Pratoomtone, Pakasit; Kongtim, Surapol; Shirai, Tomoyuki; Ito, Nobuyuki

    2001-01-01

    The present experiment was conducted to assess the influence of vitamin E, given in the diet at 0.5 or 1%, on induction of lesions in the Syrian hamster liver by long term combined administration of sodium nitrite and aminopyrine in the drinking water. Inhibition of both cholangiofibrosis and cholangiocarcinoma development, as well as a reduction in hepatocellular nodules was the result. The underlying mechanisms presumably involve alteration of endogenous dimethylnitrosamine formation by the vitamin, with clear implications for prevention in the human environment. PMID:12718657

  8. 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)

  9. Effects of H1-receptor antagonists on 14C-aminopyrine accumulated in histamine-stimulated rabbit gastric glands

    International Nuclear Information System (INIS)

    After stimulation of gastric acid production there is a considerable delay before the acid starts to appear in the gastric lumen. The present study was carried out on isolated gastric glands to test the hypothesis that there may be a mechanisms in the parietal cell that contributes to this delay by preventing emptying of the secretory canaliculi. Glands were incubated with 14C-aminopyrine and stimulated with histamine. After accumulation of 14C-aminopyrine, various concentration of H1-receptor antagonists were added. Clemastine, promethazine, and hydroxyzine effectively and cetirizine and tripelennamine less effectively decreased the accumulated 14C-aminopyrine content in a dose-dependent manner without significantly reducing the oxygen consumption. The H1-receptor antagonists influenced the 14C-aminopyrine content in another manner than H2-receptor antagonists. No effects were obtained by atropine or lidocaine, indicating that the elimination of 14C-amionopyrine is not an inticholinergic effect or due to membrane effects as exerted by local anesthetics. Stimulation of glands by further addition of histamine did not significantly stimulate the uptake of 14C-aminopyrine in the glands, whereas stimulation with db-cAMP produced an increase that was most pronounced when low concentrations of hydroxyzine had been used. It is suggested that H1-receptor antagonists do not inhibit stimulation of acid production in the secretory canaliculi. They may, however, interfere with a mechanism preventing acid from leaving the parietal cell. Such a mechanism may contribute to the delay in appearance of acid in the gastric lumen after stimulation of gastric acid production. 37 refs., 7 figs

  10. Predicting outcome of paracetamol poisoning by using 14C-aminopyrine breath test

    International Nuclear Information System (INIS)

    The 14C-aminopyrine (14C-amidopyrine) breath test, carried out within 24 to 36 hours of an overdosage of paracetamol, was used to predict the extent of liver damage in 30 seriously poisoned patients. Mean 14C02 excretion was 4.4% in 20 healthy control subjects; 5.5% in six patients who escaped injury; and 2.9%, 1.5%, and 0.2% in those with mild to moderate (12 patients), severe (eight patients), and fatal (four patients) liver damage respectively. This test proved to be a more reliable predictor of the extent of liver damage than plasma paracetamol concentration or half life or the results of conventional liver function tests and may enable treatment of hepatic failure to be started at an early stage. (author)

  11. IN VITRO EFFECT OF MITRAGYNINE (A MAJOR ALKALOID OF MITRAGYNA SPECIOSA KORTH) ON AMINOPYRINE METABOLISM IN RAT HEPATOCYTES

    OpenAIRE

    Rukhsana Anwar, Abas Hj Hussin , Sabariah Ismail* and Sharif Mahsufi Mansor

    2012-01-01

    Mitragyna speciosa Korth. is a member of the Rubiaceae family. More than 25 alkaloids have been isolated from Mitragyna speciosa. Mitragynine is the major alkaloid of this plant and is responsible for antinociceptive action. No single study is available about the effect of mitragynine on aminopyrine N-demethylase activity in rat hepatocytes. Experiments were undertaken to evaluate the effect of mitragynine in different age groups (adult & old) of Sprague- Dawley (SD) male and female rat hepat...

  12. Binding of epidermal growth factor to receptors in preparations of enriched porcine parietal cells and inhibition of aminopyrine uptake

    International Nuclear Information System (INIS)

    Preparations of isolated porcine gastric cells, enriched in parietal cells, were used to study binding of epidermal growth factor (EGF) to receptors and subsequent inhibition of (14C) aminopyrine uptake. EGF in concentrations from 10-10 to 10-7M inhibited aminopyrine uptake stimulated by 10-5M histamine with an IC50 of 3x10-10M. (125)EGF bound in a saturable and specific manner to sites on cells in preparations containing 40-90% parietal cells. Mean apparent dissociation constant for the sites was 1.6x10-9M, with an average number of approximately 20000 sites per cell. Endocytosis of ligand by parietal cells was limited, amounting to 10-20% of bound EGF after 1 h of incubation at 37oC. Occupation of a fraction of the receptors caused a maximal reduction by 40% of aminopyrine uptake in histamine-stimulated cells, suggesting the occurence of spare receptors. The results indicate the existence of specific receptors for EGF on porcine parietal cells exerting a regulatory influence on acid secretion. 28 refs., 3 figs., 1 tab

  13. IN VITRO EFFECT OF MITRAGYNINE (A MAJOR ALKALOID OF MITRAGYNA SPECIOSA KORTH ON AMINOPYRINE METABOLISM IN RAT HEPATOCYTES

    Directory of Open Access Journals (Sweden)

    Rukhsana Anwar, Abas Hj Hussin , Sabariah Ismail* and Sharif Mahsufi Mansor

    2012-07-01

    Full Text Available Mitragyna speciosa Korth. is a member of the Rubiaceae family. More than 25 alkaloids have been isolated from Mitragyna speciosa. Mitragynine is the major alkaloid of this plant and is responsible for antinociceptive action. No single study is available about the effect of mitragynine on aminopyrine N-demethylase activity in rat hepatocytes. Experiments were undertaken to evaluate the effect of mitragynine in different age groups (adult & old of Sprague- Dawley (SD male and female rat hepatocytes. In vitro this evaluation was assessed by different concentration of mitragynine (0.0025µM-250µM. Hepatocytes were prepared by collagenase perfusion technique. Aminopyrine N-demethylase activity was determined by measuring the quantity of formaldehyde formed. Results showed that a significant increase in aminopyrine N-demethylase activity was observed in the adult male, female and old female SD rat hepatocytes treated with 250µM mitragynine (p< 0.05. However, the old male rat did not show any significant change at any concentration of mitragynine. In conclusion this study indicates the induction of hepatic drug metabolizing enzymes by mitragynine is affected by the aging process in male but unaffected in female.

  14. Effects of carbachol and gastrin on [sup 14]C-aminopyrine accumulated in rabbit gastric glands and cells

    Energy Technology Data Exchange (ETDEWEB)

    Romell, B.; Seensalu, R.; Girma, K.; Nilsson, G. (Univ. of Agricultural Science, Uppsala (Sweden))

    1993-06-01

    The present study examines the possible existence of a mechanism regulating emptying of the secretory canaliculi content of the parietal cell and the possible effects of carbachol and gastrin on such a mechanism. In rabbit gastric glands stimulated with carbachol, [sup 14]C-aminopyrine accumulation reached a maximum after 15 min and then started to decrease. This decrease was not accompanied by a decrease in oxygen consumption, nor was any decrease of accumulated [sup 14]C-aminopyrine seen in dispersed gastric cells. In glands but not in cells stimulated with histamine together with 3-isobutyl-1-methylxanthine (IMX), carbachol induced a reduction in the accumulated [sup 14]C-aminopyrine content, whereas the effect of gastrin was less pronounced. The carbachol-induced reduction was counteracted by atropine, but was not accompanied by a decrease in oxygen consumption. It is suggested that there exists a mechanism that controls the emptying of the secretory canaliculi content of the parietal cell, and that carbachol, in addition to stimulating acid production, also contributes to this emptying. Paracrine factors may be involved in this latter mechanism. 13 refs., 6 figs.

  15. 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)

  16. 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.)

  17. Prostaglandin E2 inhibition of secretagogue-stimulated [14C]aminopyrine accumulation in rat parietal cells: a model for its mechanism of action

    International Nuclear Information System (INIS)

    Prostaglandin E2 (PGE2) differentially inhibited histamine and isoproterenol stimulation of [14C]aminopyrine accumulation in rat parietal cell preparations. Low concentrations of PGE2 decreased the maximum response to isoproterenol whereas higher concentrations increased the EC50 of histamine with only a modest effect on the maximum response. Also, PGE2 potentiated dibutyryl cyclic AMP stimulation of aminopyrine accumulation in either the absence or presence of carbachol. In contrast, PGE2 inhibited potentiation between carbachol and histamine due to its inhibitory effect on histamine and possibly also to an inhibitory effect on cholinergic activity. Islet activating protein prevented the inhibitory actions of PGE2. To account for these results a model is presented based on the recent proposal by Gilman of an interaction between components of adenylyl cyclase stimulatory and inhibitory guanine nucleotide binding proteins

  18. 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

  19. 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)

  20. Effect of carbon monoxide on xenobiotic metabolism in the isolated perfused rabbit lung

    Energy Technology Data Exchange (ETDEWEB)

    Trela, B.A.

    1988-01-01

    It was the aim of this study to determine the level and duration of CO exposure necessary to alter mixed function oxidase-mediated activity in the intact lung and to determine the magnitude of this effect. The effect of CO on the mixed function oxidase-mediated activities of aminopyrine, aniline, 4-ipomeanol and p-nitroanisole in isolated perfused rabbit lungs (IPRL) was investigated. Several concentrations of CO were evaluated for their effect on cytochrome P-450-mediated activity in the lung. Both artificial medium and whole blood were utilized as recirculating perfusates. Monomethyl-4-aminoantipyrine was the major metabolite of aminopyrine produced by in vitro hepatic and pulmonary preparations and by the intact lung. Ventilation of isolated rabbit lungs with 7.5% CO for 2.5 hours caused a 40% decrease in the rates of metabolism of both aminopyrine and p-nitroanisole. This level of CO exposure did not alter the cytochrome P-450-mediated metabolism of aniline nor 4-ipomeanol in the intact lung. Aminopyrine metabolism in isolated rabbit lungs perfused with whole blood was also decreased following the administration of 7.5% CO suggesting that the hemoglobin in whole blood affords no protection against CO-induced inhibition of mixed function oxidase activity in the intact lung. The isozyme of cytochrome P-450 which preferentially metabolizes aminopyrine and p-nitroanisole may be more sensitive to CO-induced inhibition than the form(s) which metabolize aniline and 4-ipomeanol.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    1994-12-31

    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.

  2. 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

  3. Autoantibody to the gastrin receptor in pernicious anemia

    International Nuclear Information System (INIS)

    The authors examined serum IgG fractions from 20 patients with pernicious anemia and 25 control subjects for their capacity to inhibit binding of [125I]15-leu human gastrin-17 to parietal-cell-enriched gastric mucosal cells. IgG fractions from six patients reduced gastrin binding by 45.6 +/- 12.2 per cent, as compared with a reduction of 1.8 +/- 0.7 per cent by fractions from the 25 controls. The fractions from these six patients also reduced gastrin-stimulated [14C]aminopyrine uptake by gastric cells (an index of gastric acid secretory activity in vitro) by 50.2 +/- 8.4 per cent (mean +/- S.D.), as compared with 9.2 +/- 4.1 per cent for the controls. IgG fractions from six other patients that did not reduce gastrin binding also inhibited gastrin-stimulated [14C]aminopyrine uptake, by 48.1 +/- 9.1 per cent. These reductions in gastrin binding and aminopyrine uptake were abolished by absorption of the IgG fractions with suspensions of viable gastric mucosal cells but not by absorption with liver or kidney cells. The IgG fractions did not inhibit [3H]histamine binding or histamine-stimulated [14C]aminopyrine uptake. These results suggest that serum IgG from some patients with pernicious anemia contains autoantibodies to the gastrin receptor

  4. 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

    2013-01-01

    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

  5. The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism.

    Science.gov (United States)

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

    2002-01-01

    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

  6. Inhibition of acid secretion from parietal cells by non-human-infecting Helicobacter species: a factor in colonization of gastric mucosa?

    OpenAIRE

    Vargas, M; Lee, A; Fox, J.G.; Cave, D. R.

    1991-01-01

    Helicobacter pylori has been shown to produce a protein that inhibits acid secretion from parietal cells. We have examined other non-human-infecting Helicobacter species for this property by measuring the uptake of [14C]aminopyrine into rabbit parietal cells as an indirect assessment of acid secretion. Helicobacter felis and an isolate from a rhesus monkey were shown to inhibit acid secretion. Isolates of Helicobacter mustelae gave variable responses. Whole bacteria and cell-free sonicates im...

  7. Effects of γ irradiation on plasma testosterone levels and hepatic drug metabolism in the rat

    International Nuclear Information System (INIS)

    When adult male Sprague-Dawley rats were exposed to whole-body irradiation of γ rays ranging from 700 to 1000 rad, oxidative demethylation of drugs such as aminopyrine was significantly reduced. In agreement with the report of McTaggart and Wills, we have independently found that this irradiation-induced inhibition of hepatic drug metabolism was a result of blockage of testosterone synthesis or release. The plasma hormone levels in the treated animals (900 rad of γ rays) declined gradually from a normal value of 5.5 +- 0.5 ng/ml to a minimum value of 0.9 +- 0.4 ng/ml, which was reached in 4 to 6 days after the irradiaton. It returned to normal level after the 10th day. This hormonal change caused by γ irradiation was parallel with the change in aminopyrine demethylation, thus suggesting that impairment of hepatic drug metabolism by γ rays was mainly secondary to the effect on the synthesis and/or release of the male sex hormone

  8. 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

    2006-01-01

    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.

  9. [Determination of six main components in compound theophylline tablet by convolution curve method after prior separation by column partition chromatography

    Science.gov (United States)

    Zhang, S. Y.; Wang, G. F.; Wu, Y. T.; Baldwin, K. M. (Principal Investigator)

    1993-01-01

    On a partition chromatographic column in which the support is Kieselguhr and the stationary phase is sulfuric acid solution (2 mol/L), three components of compound theophylline tablet were simultaneously eluted by chloroform and three other components were simultaneously eluted by ammonia-saturated chloroform. The two mixtures were determined by computer-aided convolution curve method separately. The corresponding average recovery and relative standard deviation of the six components were as follows: 101.6, 1.46% for caffeine; 99.7, 0.10% for phenacetin; 100.9, 1.31% for phenobarbitone; 100.2, 0.81% for theophylline; 99.9, 0.81% for theobromine and 100.8, 0.48% for aminopyrine.

  10. 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

    1988-01-01

    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...... 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....

  11. 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

    2011-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Biodegradation of Green HE4B: Co-substrate effect, biotransformation enzymes and metabolite toxicity analysis.

    Science.gov (United States)

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

    2010-06-01

    A high exhaust reactive dye, Green HE4B (GHE4B) was 98% degraded in nutrient medium by Pseudomonas desmolyticum NCIM 2112 (pd2112) within 72 h at static condition. Decolorization time in synthetic 10 g/l molasses. Addition of 5 g/l peptone to NaCl medium had reduced decolorization time from 108 to 72 h. Beef extract do not contribute more to the inducing effect of peptone, however it is a good co-substrate in sucrose or urea containing NaCl medium. Intracellular lignin peroxidase (Lip), laccase and tyrosinase activities were induced by 150, 355 and 212%, respectively till maximum dye removal took place. Aminopyrine N-demethylase (AND) and dichlorophenol indophenol reductase (DCIP-reductase) activities in pd2112 were induced by 130 and 20%, respectively at 72 h of incubation during GHE4B decolorization. By high performance liquid chromatography (HPLC) analysis, 4-hydroxybenzene sulfonic acid and 4-amino, 6-hydroxynaphthalene 2-sulfonic acids were identified as metabolites formed during 24-72 h incubation. Fourier transform infrared spectroscopy (FTIR) analysis supports the formation of these aromatic amines. pd2112, aerobically degraded GHE4B metabolites (formed at static condition) showing stationary phase of 6 days. There was no germination inhibition of Sorghum bicolor and Triticum aestivum by GHE4B metabolites at 3,000 ppm concentration however untreated dye showed germination inhibition at the same concentration. GHE4B metabolites did not show any microbial toxicity at 10,000 ppm concentration. PMID:23100822

  14. Discrimination and quantification of cocaine and adulterants in seized drug samples by infrared spectroscopy and PLSR.

    Science.gov (United States)

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

    2015-12-01

    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

  15. Medical application of stable isotopes

    International Nuclear Information System (INIS)

    The application of stable isotopes (SI) to clinical examinations was reviewed. As an example of 14C-breath test, the application of 1-14C-cholate to intestinal bacterial overgrowth syndrome was described, and as an example of 13C-breath test, the application of glycine-1-13C-cholate. The breath test using 13C-galactose and 13C-aminopyrine was applied to liver function tests, that using 13C-trioctanoin, fat absorption test, and that using 13C-glycine and 13C-glucose, congenital abnormalities of metabolism. Moreover, studies of sugar metabolism by means of glucose labelled with SI and protein N metabolism by means of compounds labelled with 15N were reported. Measurement of pulmonary extravascular fluid by heavy water, respiratory function test by 4He gas, and movement of bile acid by 2H-bile acid were also reported. The application of SI to metabolic route examination and serum in vitro examination was also described. (Kanao, N.)

  16. Induction of diphenytriazol on cytochrome CYP1A

    Institute of Scientific and Technical Information of China (English)

    Yun-zhen HU; Tong-wei YAO

    2004-01-01

    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.

  17. Pulmonary uptake of morphine (M)

    International Nuclear Information System (INIS)

    Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H2O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium within 4 min. At equilibrium lung/perfusate conc. ratios for H2O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H2O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H2O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs

  18. Effects of proximal gastric vagotomy and antrectomy on parietal cell function in humans

    International Nuclear Information System (INIS)

    Both proximal gastric vagotomy and antrectomy reduce maximal gastric acid secretion in vivo by about 60%. The combination of vagotomy and antrectomy reduces the maximal acid secretion by about 80%. This additive effect indicates that these surgical procedures differ in their mode of action. The function of isolated human oxyntic glands was studied before and after vagotomy and antrectomy, respectively, using radioactively labeled aminopyrine as a marker of parietal cell response. The basal accumulation increased after vagotomy, suggesting a vagally controlled inhibitory component. The carbachol response disappeared and the maximal response induced by histamine or dibutyryl-cyclic adenosine monophosphate was reduced by 60% (p less than 0.01) after vagotomy. This reduction could not be overcome by increasing the dose of dibutyryl-cyclic adenosine monophosphate. This indicates an intracellular effect of vagotomy peripheral to dibutyryl-cyclic adenosine monophosphate point of action. Antrectomy did not induce any statistically significant change at the glandular level, indicating that the reduced gastric acid secretion in vivo may be caused by a reduction in the number of oxyntic glands due to a removal of a trophic effect of antral gastrin

  19. 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.

    Science.gov (United States)

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

    2000-09-10

    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

  20. The hepatoprotective cytochrome P-450 enzyme inhibitor isolated from the Nigerian medicinal plant Cochlospermum planchonii is a zinc salt.

    Science.gov (United States)

    Aliyu, R; Okoye, Z S; Shier, W T

    1995-10-01

    Aqueous extracts of Cochlospermum planchonii Hook.f. (Cochlospermaceae) rhizomes are used by native medical practitioners in northern Nigeria to treat jaundice. An extract prepared by a laboratory adaptation of their method was hepatoprotective in carbon tetrachloride-treated rats (CCl4), and it inhibited cytochrome P-450 enzymes, which constitutes a plausible hepatoprotective mechanism. A crystalline inhibitor (0.3% of dry weight of rhizomes) was isolated using inhibition of two rat cytochrome P-450 enzymes, aminopyrine-N-demethylase and aniline hydroxylase, as bioassays to guide fractionation by solvent partitioning, polyamdie column chromatography, preparative thin layer chromatography and fractional crystallization. The inhibitor was identified as zinc formate by inductively coupled plasma atomic emission spectroscopy, nuclear magnetic resonance spectroscopy and comparison with synthetic material by power X-ray diffraction crystallography. Synthetic and plant-derived zinc formate were equally effective as inhibitors of cytochrome P-450 enzymes and as hepatoprotective agents in carbon tetrachloride-treated rats. Cochlospermum planchonii rhizomes contain unusually high levels of manganese and zinc, although much higher levels have been observed in plants considered to be hyperaccumulators of these metals. PMID:8583799

  1. 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

    2005-01-01

    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.

  2. Comparative expression of liver cytochrome P450-dependent monooxygenases in the horse and in other agricultural and laboratory species.

    Science.gov (United States)

    Nebbia, C; Dacasto, M; Rossetto Giaccherino, A; Giuliano Albo, A; Carletti, M

    2003-01-01

    The apoprotein expression and the catalytic activities of cytochrome P450s involved in the biotransformation of xenobiotics were investigated in horse liver microsomes and compared with those of food producing (cattle, pigs, broiler chicks, and rabbits) and laboratory species (rats). Western blot analysis revealed the presence of proteins immunorelated to rat CYP 1A, CYP 2B, CYP 2E, and CYP 3A subfamilies in hepatic microsomes from horses and from any other examined species. With the exception of the N-demethylation of N-nitrosodimethylamine in broiler chicks, all the recorded interspecies differences were quantitative in nature. Equine preparations proved the most active in the biotransformation of the CYP 1A substrates ethoxy- and methoxyresorufin and the least active in the metabolism of aminopyrine and ethoxycoumarin. On a comparative basis, large differences were observed in the rate of the in vitro metabolism of model substrates between "minor" (rabbits, horses) and "major" food producing species. Taken in due consideration the limitations of the in vitro approach, results from this study reinforce the conclusion that studies on drug efficacy and residue depletion should be performed in each target species. PMID:12618071

  3. 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

    2015-01-01

    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

  4. Primary culture of secretagogue-responsive parietal cells from rabbit gastric mucosa

    International Nuclear Information System (INIS)

    A new procedure for isolation and primary culture of gastric parietal cells is described. Parietal cells from rabbit gastric mucosa are enriched to greater than 95% purity by combining a Nycodenz gradient separation with centrifugal elutriation. Cells are plated on the basement membrane matrix, Matrigel, and maintained in culture for at least 1 wk. Parietal cells cultured in this manner remain differentiated, cross-react with monoclonal H+-K+-ATPase antibodies, and respond to histamine, gastrin, and cholinergic stimulation with increased acid production as measured by accumulation of the weak base, [14C]aminopyrine. When stimulated, cultured cells undergo ultrastructural changes in which intracellular canaliculi expand and numerous microvilli are observed. These ultrastructural changes are similar to those previously found to occur in vivo and in acutely isolated parietal cells. Morphological transformations in living cells can also be observed with differential interference contrast optics in the light microscope. After histamine stimulation, intracellular canaliculi gradually expand to form large vacuolar spaces. When the H2 receptor antagonist, cimetidine, is added to histamine-stimulated cells, these vacuoles gradually disappear. The ability to maintain hormonally responsive parietal cells in primary culture should make it possible to study direct, long-term effects of a variety of agonists and antagonists on parietal cell secretory-related activity. These cultured cells should also prove to be useful for the study of calcium transients, ion fluxes, and intracellular pH as related to acid secretion in single cells, particularly since morphological transformations can be used to monitor physiological responses at the same time within the same cell

  5. Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate.

    Science.gov (United States)

    Hiramatsu, N; Kishida, T; Natake, M

    1989-08-01

    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

  6. Influence of diet and nutritional status on drug metabolism.

    Science.gov (United States)

    Walter-Sack, I; Klotz, U

    1996-07-01

    Genetic and environmental factors contribute to a wide inter- and intraindividual variability in drug metabolism. Among the environmental factors that may influence drug metabolism, the diet and nutritional status of the individuals are important determinants. As altered drug-metabolising enzyme activities can influence the intensity and duration of drug action, such factors should be considered in pharmacotherapy. For this reason the effects of dietary energy, protein deficiency, nutritional ingredients, special diet forms and nutrition regimens and malnutritional states must be differentiated. In various pharmacokinetic studies different model drugs metabolised either by oxidative phase I pathways [e.g. phenazone (antipyrine), aminopyrine, phenacetin, theophylline, propranolol, nifedipine] or phase II conjugation reactions [e.g. paracetamol (acetaminophen), oxazepam] were used and from the calculated pharmacokinetic data some information on the involved and affected drug-metabolising enzymes [e.g. cytochrome P450 (CYP) subspecies, glucuronosyltransferases] can be generated. It is well known that smoking, charcoal broiled food or cruciferous vegetables induce the metabolism of many xenobiotics, whereas grapefruit juice increases the oral bioavailability of the high clearance drugs nifedipine, nitrendipine or felodipine by inhibiting their presystemic (intestinal) elimination. Energy deficiency, and especially a low intake of protein, will cause a decrease of about 20 to 40% in phenazone and theophylline clearance and elimination of those drugs can be accelerated by a protein-rich diet. In the same way, protein deficiency induced by either vegetarian food or undernourishment will have the opposite pharmacokinetic consequences. On the basis of some more examples from the literature it is emphasised that the variable influence of the above factors should be taken into account in study participant selection and study design when the pharmacokinetics of a drug must be

  7. Biodegradation of crystal violet by Agrobacterium radiobacter.

    Science.gov (United States)

    Parshetti, G K; Parshetti, S G; Telke, A A; Kalyani, D C; Doong, R A; Govindwar, S P

    2011-01-01

    Agrobacterium radiobacter MTCC 8161 completely decolorized the Crystal Violet with 8 hr (10 mg/L) at static anoxic conditions. The decreased decolorization capability by A. radiobacter was observed, when the Crystal Violet concentration was increased from 10 to 100 mg/L. Semi-synthetic medium containing 1% yeast extract and 0.1% NH4C1 has shown 100% decolorization of Crystal Violet within 5 hr. A complete degradation of Crystal Violet by A. radiobacter was observed up to 7 cycles of repeated addition (10 mg/L). When the effect of increasing inoculum concentration on decolorization of Crystal Violet (100 mg/L) was studied, maximum decolorization was observed with 15% inoculum concentration. A significant increase in the activities of laccase (184%) and aminopyrine N-demethylase (300%) in cells obtained after decolorization indicated the involvement of these enzymes in decolorization process. The intermediates formed during the degradation of Crystal Violet were analyzed by gas chromatography and mass spectroscopy (GC/MS). It was detected the presence of N,N,N',N"-tetramethylpararosaniline, [N, N-dimethylaminophenyl] [N-methylaminophenyl] benzophenone, N, N-dimethylaminobenzaldehyde, 4-methyl amino phenol and phenol. We proposed the hypothetical metabolic pathway of Crystal Violet biodegradation by A. radiobacter. Phytotoxicity and microbial toxicity study showed that Crystal Violet biodegradation metabolites were less toxic to bacteria (A. radiobacter, P. aurugenosa and A. vinelandii) contributing to soil fertility and for four kinds of plants (Sorghum bicolor Vigna radiata, Lens culinaris and Triticum aestivum) which are most sensitive, fast growing and commonly used in Indian agriculture. PMID:22128547

  8. Toxicity of ultraviolet-irradiated halothane in mice

    International Nuclear Information System (INIS)

    Some operating rooms are equipped with ultraviolet (u.v.) radiating germicidal lamps which can decompose halocarbons. One such agent is the widely used anesthetic, halothane. To study the toxicity of u.v. decomposed halothane, mice were exposed to anesthetic concentrations (1.3%) of non- and u.v.-irradiated halothane in oxygen for 90 min. Halothane sleeping times increased from 14.3 min to 72.5 min. Microsomal mixed function oxidase activity decreased, as shown by prolonged pentobarbital sleeping times 1 day after exposure to halothane and irradiated halothane (54.6 min and 149.1 min, respectively, as compared to a 34.6-min control). Quantitative and qualitative differences were found in the amount of (14C)-pentobarbital metabolites excreted by u.v. irradiated halothane-exposed mice compared to either oxygen or non-irradiated halothane-exposed groups. In addition, serum glutamic-oxalacetic transaminase (SGOT) of irradiated halothane-exposed mice increased to 233% of the control values, and serum glutamic-pyruvic transaminase (SGPT) were 377% of control values. No significant changes in SGOT or SGPT occurred in non-irradiated halothane-exposed mice. Hepatic cytochromes P-450 and b5 decreased 20% and 13%, respectively, in animals exposed to irradiated halothane, with no significant change in mice exposed to non-irradiated halothane. Microsomal aminopyrine demethylase activity in irradiated halothene-exposed mice also fell to 74% of the control or non-irradiated group values. Decomposition was approximately 10-fold greater for halothane irradiated in oxygen than in nitrogen. Inorganic bromine and fluorine were present, and 9 compounds were recognized by gas-liquid chromatography. Debromination and formation of 2,2, 2-trifluoroacetyl chloride on irradiation in air are hypothesized to be responsible for the increased toxicity. Studies are in progress to evaluate the toxicity of lower concentrations for longer periods and to identify further the decomposition products

  9. Pulmonary uptake of morphine (M)

    Energy Technology Data Exchange (ETDEWEB)

    Roerig, D.L.; Bunke, S.S.; Kotrly, K.J.; Dawson, C.A.; Kampine, J.P.

    1986-03-01

    Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H/sub 2/O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium within 4 min. At equilibrium lung/perfusate conc. ratios for H/sub 2/O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H/sub 2/O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H/sub 2/O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs.

  10. 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,

    2003-01-01

    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 mg.kg-1.d-1 (n=20) and 83.3 mg.kg-1@d-1 (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 nmol.mg MS pro-1) were significantly increased compared with the control group (1.08±1.04, 5.51±2.98nmol.mg 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 mmol.mg 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.

  11. Inhibition of the gastric H+,K+ -ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews.

    Science.gov (United States)

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

    2007-04-20

    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

  12. 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

  13. 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

  14. Effects of bromocriptine on hepatic cytochrome P-450 monooxygenase system.

    Science.gov (United States)

    Moochhala, S M; Lee, E J; Hu, G T; Koh, O S; Becket, G

    1989-02-01

    We have evaluated the in vitro effects of bromocriptine (Br), on the hepatic cytochrome P-450 monooxygenase system of rats pretreated with saline phenobarbitone (PB) and beta-naphthoflavone (BNF). Br inhibited ethoxyresorufin O-dealkylase (EROD) activity in liver microsomes of rats pretreated with saline and PB but not in BNF pretreated animals. Maximum inhibition of EROD activity by Br in the microsomes of saline and PB pretreated rats were 50%-60% of the control. In contrast, a dual effect was observed on aminopyrine N-demethylase activity (APD) by Br in microsomes of saline, PB and BNF pretreated rats. At a low concentration (25 microM), Br inhibited the activity of APD to a similar extent in all pretreatment groups; however, with higher concentrations of Br (50 microM to 300 microM), enhancement of APD activity was observed. Br (300 microM) increased the APD activity to 2-3 times the control level in microsomes of rats pretreated with saline, PB or BNF. Spectral studies revealed a Type II binding of Br to cytochrome P-450 from microsomes of saline and PB pretreated rats. A reverse type I binding was observed for BNF induced microsomes. In addition, Br also enhanced NADPH cytochrome c (P-450) reductase activity to a similar extent in all pretreatment groups. These results suggest that the inhibition of EROD activity may be due to direct binding by Br to certain isozymes of cytochrome P-450 and that the enhancing effect of Br on APD activity may be in part due to the activation of the NADPH cytochrome c reductase component of the cytochrome P-450 monooxygenase system. PMID:2499727

  15. Hepatic calcium efflux during cytochrome P-450-dependent drug oxidations at the endoplasmic reticulum in intact liver.

    Science.gov (United States)

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

    1981-06-01

    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

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

    Directory of Open Access Journals (Sweden)

    Yi ZHANG

    2012-11-01

    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

  17. Gene response of CYP360A, CYP314, and GST and whole-organism changes in Daphnia magna exposed to ibuprofen.

    Science.gov (United States)

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

    2016-01-01

    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

  18. 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

    2013-01-01

    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

  19. 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)

    隋译

    2016-01-01

    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。

  20. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment

    International Nuclear Information System (INIS)

    Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A2 (cPLA2) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg-1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA2 in the

  1. 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

    2011-01-01

    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

  2. STUDY ON THE ATTACK CONTROL ACTION OF ELECTRO-ACUPUNCTURE ON T(A)IY(A)NG(太阳 EX-HN5)FOR MIGRAINE DUE TO HYPERACTIVITY OF LIVER YANG:RANDOMIED CONTROLED TRIAL%电针太阳穴治疗偏头痛肝阳上亢证的控制发作效应研究

    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

    2008-01-01

    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