Wyniki wyszukiwania - Biblioteka Nauki

1

Metabolic activation of adriamycin by NADPH-cytochrome P450 reductase; overview of its biological and biochemical effects.

100%

Bartoszek A.

Acta Biochimica Polonica

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2002

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tom 49

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nr 2

323-331

EN

NADPH-cytochrome P450 reductase (P450 reductase) is one of the enzymes implicated in the metabolism of adriamycin, a very important clinically used antitumour drug. However, apart from the enzyme involvement, so far little was known about the chemical route and biochemical effects of this process. We demonstrated that the application of P450 reductase simultaneously with adriamycin to tumour cells in culture significantly increased cytotoxicity of the drug. Under tissue culture conditions, we noticed also that, in the presence of P450 reductase, adriamycin metabolite(s), displaying an altered spectrum within the visible light range were formed. This observation was taken adavantage of to study the metabolism of adriamycin in cell-free systems, using initially the enzyme isolated from rat liver and the recently obtained recombinant human P450 reductase. The reductive conversion of the drug turned out to be a multi-stage process, which occurred only under aerobic conditions and was accompanied by excessive NADPH consumption. Further research carried out with the aid of radical scavengers and radiolabelled adriamycin revealed that the enhancement of biological activity of adriamycin by P450 reductase stemmed from the formation of alkylating metabolite(s) rather than from the promotion of redox cycling known to be induced in the presence of anthracyclines.

2

Apoptotic index and histological assessment of renal tubular epithelial cells during anthracycline-induced apoptosis. Influence of time

75%

Pedrycz A. , Boratynski Z. , Drelich G.

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2010

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tom 54

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nr 1

55-58

EN

The presented study describes renal tubular epithelial cells morphology in rats during adriamycin therapy. It was demonstrated that one dose of the compound can induce increasing-with time-apoptosis in the cells. A statistically-significant increase in the number of apoptotic cells was observed in experimental groups compared to controls. The highest percentage of apoptotic cells was found in rats 7 weeks after adriamycin administration. The number of apoptotic cells in these animals was statistically significantly higher than that in the rats 4 weeks after adriamycin administration.

3

A transferrin conjugate of adriamycin-synthesis and potential chemotherapeutic efficacy

75%

Lubgan D. , Jozwiak Z.

Cellular and Molecular Biology Letters

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2002

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tom 07

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nr Suppl.

4

Effect of H2O2 on adriamycin-induced cytotoxicity in vitro

75%

Anuszewska E. L.

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tom 42

|

nr 4

5

The influence of adriamycin on the CD4 and CD8 cells in the course of trichinellosis in mice

75%

Karmanska K. , Houszka M. , Mista D. , Stefaniak E.

Wiadomości Parazytologiczne

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1994

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tom 40

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nr 4

EN

The effect of adriamycin on the behaviour of CD4⁺ and CD8⁺ cells in the course of trichinellosis in mice has been studied. The animals infected with 200 larvae per mouse were administered intraperitoneally adriamycin (Adriblastin from Farmitalia) at 1st and 28th day post infection (dpi), in a dosis of 0.2 mg. The mice were killed weakly for 6 weeks and then at the 60th dpi. The examinations were made on histologic sections from the spleen, mesenteric lymph node, jejunum and masseter muscle using immunofluorescent and immunoenzymatic methods with monoclonal antibody. The mice receiving adriamycin exhibited more CD8⁺ cells in the intestinal mucosa and by the end of the experiment also in the muscles in comparison with the control animals, which, however, did not affect the course of the infection.

6

The effect of new anthracycline derivatives on the induction of apoptotic processes in human neoplastic cells

75%

Gruber B. M. , Anuszewska E. L. , Priebe W.

Folia Histochemica et Cytobiologica

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2004

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tom 42

|

nr 2

7

Capability of adriamycin and busulfan to induce adaptive response in vitro

75%

Anuszewska E. L. , Koziorowska J. H.

Archivum Immunologiae et Therapiae Experimentalis

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1999

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tom 47

|

nr 1

8

DNA damage and repair in normal and neoplastic cells treated with adriamycin

75%

Anuszewska E. L. , Gruber B.

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nr 4

XX

Adriamycin (ADR), a common antineoplastic drug, was used to study DNA repair synthesis, cell cytotoxicity and DNA single strand breaks in normal human fibroblasts — CLV98 and human melanoma cells — ME18. No repair synthesis was observed in ME18 and CLV98 cells exposed to adriamycin in concentrations up to 10~5 M. ME18 cells were less sensitive to ADR treatment than CLV98 cells. Adriamycin-induced DNA single strand breaks (at ADR concentration: 1 pg/ml) were incompletely repaired in ME18 cells and unrepaired in CLV98 cells within 24 h after drug removal. Within 48 h strand breaks were completely repaired in both kinds of cells. No repair of single strand breaks was observed in ME18 and CLV98 cells after drug treatment in the concentration of 5 Jig/ml.

9

Immunolocalization in portal acinus of the liver of different types of adriamycin induced cell death depending on time

63%

Pedrycz A. , Boratynski Z. , Mendocha J.

Medycyna Weterynaryjna

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2014

|

tom 70

|

nr 02

EN

The ability to control the phenomenon of apoptosis, its induction or inhibition, raises hopes for treating many diseases including cancer. Adriamycin, an antibiotic that is wildly used after treating cancer, induces apoptosis in liver cells in a certain and relatively quick way after its application. The aim of the work was to obtain and examine the model of apoptosis and necrosis of hepatocytes with respect to their response to different damaging stimuli (adriamycin) depending on the time after the application in correlation with the ultrastructural construction, which is the result of the different location of hepatocytes within the portal acinus (of Rappaport). There were 32 female white Wistar rats used in the study. They were divided into 4 groups (2 experimental and 2 control), 8 animals in each group. The adriamycin dose of 5 mg/kg was administered intraperitoneally to the rats in groups I and II and then the rats were decapitated after 4 weeks (group I) and after 8 weeks (group II). The rats in the control groups were given 0.5 ml 0.9% NaCl solution and then decapitated after 4 weeks (group III) and 8 weeks (group IV). In the research, preparations made from fragments of the right liver lobe were used for histological observations and immunohistochemical studies. In the immunohistochemical studies, a three-stage method was used. According to this method, hepatocytes were examined qualitatively and quantitatively for the presence of proteins involved in apoptosis, to which the death signals run: through mitochondrial pathways (caspase 3 and caspase 9), through intrinsic pathways by endoplasmic reticulum (caspase 3 and caspase 12), through extrincic pathways (caspase 3 and caspase 8) and one from inflammatory markers: caspase 1. Histological images showed that the apoptosis phenomenon occurs after the administration of adriamycin in hepatocytes in a zonate way and is dependent on the time that has elapsed since its administration. Immunohistochemical studies showed, in both a qualitative and quantitative way, a phenomenon of apoptosis in hepatocytes (executive caspase 3) and necrosis (caspase 1). It was also proved that the signal for the induction of apoptosis showed zonation and mainly followed the mitochondrial pathway (caspase 9); the intrinsic pathway by endoplasmic reticulum was much less common (caspase 12); while even more rarely caspase 8 was identified as a marker of an extrinsic pathway to induce apoptosis.

10

Metabolic activation of adriamycin by NADPH-cytochrome P450 reductase; overview of its biological and biochemical effects

63%

Bartoszek A.

Acta Biochimica Polonica

|

2002

|

tom 49

|

nr 2

EN

NADPH-cytochrome P450 reductase (P450 reductase) is one of the enzymes implicated in the metabolism of adriamycin, a very important clinically used antitumour drug. However, apart from the enzyme involvement, so far little was known about the chemical route and biochemical effects of this process. We demonstrated that the application of P450 reductase simultaneously with adriamycin to tumour cells in culture significantly increased cytotoxicity of the drug. Under tissue culture conditions, we noticed also that, in the presence of P450 reductase, adriamycin metabolite(s), displaying an altered spectrum within the visible light range were formed. This observation was taken adavantage of to study the metabolism of adriamycin in cell-free systems, using initially the enzyme isolated from rat liver and the recently obtained recombinant human P450 reductase. The reductive conversion of the drug turned out to be a multi-stage process, which occurred only under aerobic conditions and was accompanied by excessive NADPH consumption. Further research carried out with the aid of radical scavengers and radiolabelled adriamycin revealed that the enhancement of biological activity of adriamycin by P450 reductase stemmed from the formation of alkylating metabolite(s) rather than from the promotion of redox cycling known to be induced in the presence of anthracyclines.

11

Heat shock protein 70 as a marker of oxygen stress in kidneys of rat offspring. Immunohistochemical assessment

63%

Pedrycz A. , Boratynski Z. , Visconti J.

Bulletin of the Veterinary Institute in Puławy

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2006

|

tom 50

|

nr 2

12

L-arginine decreases heat shock protein 70 [marker of environmental stress] expression in kidney cells of rat fetuses during apoptosis - late effect of adriamycin action

63%

Pedrycz A. , Brzeski Z.

Annals of Agricultural and Environmental Medicine

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2006

|

tom 13

|

nr 1

EN

Both Adriamycin and nitric oxide (NO) cause apoptosis acting through or as free radicals inciting oxidative stress in the cell. However, in some tissues the antiapoptotic action of NO was described, thereby the impact of NO on cell apoptosis is not finally recognized. In this study, a trial of the evaluation of exogenous NO (L-arginine) impact on apoptosis induced by Adriamycin in fetal kidney cells was undertaken. For this reason, the expression of Heat Shock Protein 70 (HSP 70), environmental stress marker, as a sensitive biomarker of oxidative stress induced in fetal kidney cells with Adriamycin given to mothers prior to pregnancy was studied using immunohistochemical method. The expression of HSP 70 in fetal kidney cells, whose mothers received apart from Adriamycin, L-arginine (as NO substrate) was also evaluated. The results of the study pointed to the fact that the exogenous NO (L-arginine) could be helpful in inhibition of intensified apoptosis in fetal cells as a late effect of Adriamycin action.

13

Effect of adriamycin and gamma-radiation on cultured mammalian cells measured by flow cytometry

63%

Koceva-Chyla A. , Distel L. , Zaborowski A. , Skierski J. , Rozga B. , Schussler H. , Jozwiak Z.

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tom 18

|

nr 2

14

DNA repair of adriamycin induced damage in mouse and human cells differing in catalase activity

63%

Gruber B. M. , Anuszewska E. L.

Acta Biochimica Polonica

|

1998

|

tom 45

|

nr 2

EN

Catalase is known to counteract cytotoxic effect of adriamycin, used as an anti-neoplastic drug. In cells with low catalase activity no repair of adriamycin induced lesions was observed up to 48 h post treatment. In cells with high catalase activity after 48 h the repair was either complete or partial depending on the human or mouse cell type used.

15

Apoptosis of foetal renal tubular epithelial cells as late effect of adriamycin action. Immunohistochemical assessment of caspase 3 expression

63%

Pedrycz A. , Boratynski Z. , Wieczorski M. , Czerny K.

Bulletin of the Veterinary Institute in Puławy

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2007

|

tom 51

|

nr 1

EN

In previous papers, we noticed that adriamycin given to female rats before their planned pregnancy has a delaying effect under the form of apoptosis for foetal hepatocytes. The purpose of present study was for a quantitative assessment of foetal renal tubular epithelial cells, as an effect means of delaying adriamycin action (apoptotic index). Expression of effector caspase 3 was also assessed. In the investigations, a standard three-step immunohistochemical method was used. The area covered by positive caspase 3 reaction was examined. In the kidneys of foetuses from the experimental group, we noticed an increase in the apoptotic index; furthermore, immunohistochemical reaction for caspase 3 covered a statistically significantly larger range as compared to the control group. The delayed effect of adriamycin, which was given to female rats before pregnancy, was an increase in apoptosis in foetal renal tubular epithelial cells.

16

Ultrastructural evaluation of renal convoluted tubules of female rats, which had pregnancy complicated with secondary preeclampsia

51%

Pedrycz A. , Wieczorski M. , Boratynski Z. , Czerny K. , Flieger S.

Electronic Journal of Polish Agricultural Universities. Series Veterinary Medicine

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2005

|

tom 08

|

nr 2

17

P-53 protein and proteins from BCL-2 family in the heart of rat after adriamycin administration. Immunohistochemical evaluation

51%

Boratynski Z. , Pedrycz A.

Electronic Journal of Polish Agricultural Universities. Series Veterinary Medicine

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2006

|

tom 09

|

nr 2

EN

Adriamycin (ADR) – the antineoplastic antibiotics has confirmed proapoptotic activity, mainly on neoplastic cells and young quick dividing cells. Cardiotoxicity of Adriamycin is limitating in antineoplastic therapy. The purpose of study was an evaluation of internal pathway of induction of signal to the apoptosis in myocardial cells of rat, which had administered Adriamycin. The sign of late cardiotoxicity after Adriamycin is coagulative necrosis. In present study was noticed also increased apoptosis of cells in rat heart, which was induced via mitochondrial pathway, with activation of p-53 protein and with BAX/Bcl-2 ratio > 1 – with prevalence of proapoptotic BAX protein.

18

The ability of new formamidine sugar-modified derivatives of daunorubicin to stimulate free radical formation in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome p450 reductase and xanthine oxidase

51%

Pawlowska J. , Tarasiuk J. , Borowski E. , Wasowska M. , Oszczapowicz I. , Wolf C. R.

Acta Biochimica Polonica

|

2000

|

tom 47

|

nr 1

EN

Some sterically hindered N-substituted derivatives of daunorubicin are known to be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase. In consequence, poor oxygen radical generation by these compounds is observed. In this study we examined a new family of sugar-N-substituted derivatives of daunorubicin bearing a bulky substituent introduced on the nitrogen atom through the amidine spacer. These compounds were found to be very active in radical formation catalyzed by all three studied enzymes. Thus, the introduction of a heterocyclic ring, even if it is bulky but flexible, on the nitrogen atom of daunosamine moiety through the one-atom spacer (amidine group), does not induce the steric hindrance effect on the interaction of daunorubicin derivatives with these flavoprotein enzymes.

19

Doksorubicyna i chlorowodorek doksorubicyny – frakcja wdychalna : dokumentacja proponowanych dopuszczalnych wielkości narażenia zawodowego

44%

Kupczewska-Dobecka M.

Podstawy i Metody Oceny Środowiska Pracy

|

2020

|

tom Nr 1 (103)

35--70

PL

Doksorubicyna (CAS: 23214-92-8) i jej chlorowodorek (CAS: 25136-40-9) to organiczne substancje chemiczne rozpuszczalne w wodzie. Doksorubicyna to lek cytostatyczny z grupy antybiotyków antracyklinowych, stosowany w antymitotycznej chemioterapii antynowotworowej, przede wszystkim drogą dożylną, dopęcherzowo, a także, w przypadku raka płuca, w postaci aerozolu do inhalacji. W Polsce, według informacji z Centralnego Rejestru Danych o Narażeniu na Substancje Chemiczne, ich Mieszaniny, Czynniki lub Procesy Technologiczne o Działaniu Rakotwórczym lub Mutagennym, prowadzonego w Instytucie Medycyny Pracy w Łodzi, liczba osób narażonych łącznie na doksorubicynę i jej chlorowodorek w 2016 r. wynosiła 587 Podawanie doksorubicyny lub jej chlorowodorku pacjentom w dawkach leczniczych może prowadzić do: mielosupresji, kardiomiopatii i zwłóknienia mięśnia sercowego oraz neurotoksyczności. Najmniejsza dawka terapeutyczna po podaniu doksorubicyny wziewnie w postaci aerozolu w badaniach klinicznych pacjentom z chorobą nowotworową wynosi 0,04 mg/kg mc. Skutki niepożądane podania doksorubicyny obejmowały: kaszel, duszność, ból w klatce piersiowej, świszczący oddech, chrypkę, krwioplucie oraz skurcz oskrzeli. Toksyczność ogólnonarządowa była określona jako łagodna i przejściowa i obejmowała: ból gardła, anoreksję, zaburzenia smaku, zmęczenie, nudności, ból języka i tachykardię. Producenci doksorubicyny w kartach charakterystyki podają, że narażenie inhalacyjne na pył lub aerozol jest niebezpieczne dla zdrowia, może powodować: dyskomfort, nudności, wymioty, supresję szpiku kostnego, zapalenie jamy ustnej, utratę włosów i kardiotoksyczność. W badaniach rakotwórczości przeprowadzonych na zwierzętach wykazano, że doksorubicyna była rakotwórcza dla szczurów po podaniu dożylnym i podskórnym, powodując głównie guzy gruczołu sutkowego. Stwierdzono działanie genotoksyczne doksorubicyny na komórki somatyczne i zarodkowe myszy. Zaobserwowano aberracje chromosomowe w komórkach szpiku kostnego. Doksorubicyna działa szkodliwie na rozrodczość. Może działać szkodliwie na płodność i na dziecko w łonie matki. W Polsce oraz w innych państwach dotychczas nie zostały ustalone wartości najwyższych dopuszczalnych stężeń doksorubicyny i jej chlorowodorku w środowisku pracy. Dopuszczalne poziomy narażenia zawodowego rekomendują jej producenci: FormuMax Scientific, Inc. oraz Pfizer, na poziomie 0,0005 mg/m³ . Zaproponowano przyjąć wartość NDS doksorubicyny i jej chlorowodorku na poziomie stężenia ekwiwalentnego do 0,1% najmniejszej znalezionej w piśmiennictwie wziewnej dawki terapeutycznej u ludzi Dw = 0,04 mg/kg mc., tj. na poziomie 0,0003 mg/m³ – frakcja wdychalna. Nie ma podstaw merytorycznych do ustalenia wartości najwyższego dopuszczalnego stężenia chwilowego (NDSCh). Zalecono oznakowanie substancji notacją „skóra” – wchłanianie substancji przez skórę może być tak samo istotne, jak przy narażeniu drogą oddechową. Należy również zastosować oznakowanie literami „Ft” – substancja o działaniu szkodliwym na rozrodczość, Carc. 1B – substancja rakotwórcza kategorii zagrożenia 1B oraz Muta. 1B – substancja mutagenna na komórki rozrodcze kategorii zagrożenia 1B. Zakres tematyczny artykułu obejmuje zagadnienia zdrowia oraz bezpieczeństwa i higieny środowiska pracy będące przedmiotem badań z zakresu nauk o zdrowiu oraz inżynierii środowiska.

EN

Doxorubicin (CAS: 23214-92-8) and its hydrochloride (CAS: 25136 40 9) are organic chemicals soluble in water. It is a cytostatic drug from the group of anthracycline antibiotics, used in antimitotic antitumor chemotherapy, primarily by intravenous, intravesical, and also in the case of lung cancer in the form of an aerosol for inhalation. In Poland, according to data from the Central Data Register on Exposure to Chemicals, Mixtures Thereof, Factors or Technological Processes with Carcinogenic or Mutagenic Effect, conducted at the Institute of Occupational Medicine in Łódź, the number of people exposed to doxorubicin and its hydrochloride in 2016 totaled 587. Administration of doxorubicin or its hydrochloride to patients at therapeutic doses may lead to myelosuppression, cardiomyopathy and myocardial fibrosis as well as neurotoxicity. Adverse effects of doxorubicin administration included cough, shortness of breath, chest pain, wheezing, hoarseness, hemoptysis, and bronchospasm. Systemic toxicity was defined as mild and transient and included sore throat, anorexia, dysgeusia, fatigue, nausea, tongue pain, tachycardia. Doxorubicin manufacturers state in their safety data sheets that inhalation of dust or aerosol is hazardous to health, may cause discomfort and nuisance, nausea, vomiting, bone marrow suppression, stomatitis, hair loss, and cardiotoxicity. Animal carcinogenicity studies have shown that doxorubicin was carcinogenic to rats after intravenous and subcutaneous administration, mainly causing mammary gland tumors. Doxorubicin has been shown to have genotoxic effects on somatic and embryonic mouse cells. Doxorubicin is toxic for reproduction. It may damage fertility and the unborn child. In Poland and in other countries, the highest permissible concentrations of doxorubicin and its hydrochloride in the work environment have not yet been determined. Occupational exposure limits are recommended by its manufacturers: FormuMax Scientific, Inc. and Pfizer at 0.0005 mg/m³ . It was proposed to set up the MAC value for doxorubicin and its hydrochloride at the equivalent concentration level up to 0.1% of the lowest inhalational therapeutic dose found in the literature Dw = 0.04 mg/kg, i.e., 0.0003 mg/m³ – inhalable fraction. There are no substantive grounds to determine the STEL value. It is recommended to label the substance with the notation “skin” – the absorption of the substance through the skin may be just as important as when inhaled. The letters “Ft” should also be used – toxic for reproduction, Carc. 1B – carcinogen category 1B and Muta. 1B – germ cell mutagen category 1B. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.