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LOSS OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 1 (MRP1/ABCC1) POTENTIATES DOXORUBICIN-INDUCED CARDIOTOXICITY IN MICEZhang, Wei 01 January 2015 (has links)
Doxorubicin (DOX) is a broad-spectrum and effective chemotherapeutic agent, but its use in oncologic practice is limited by dose-dependent cumulative cardiotoxicity. DOX-induced cardiotoxicity is in large part due to its ability to cause oxidative stress. Multidrug resistance associated protein 1 (MRP1/ABCC1) is a member of the ATP-binding cassette (ABC) transporter superfamily. By effluxing a wide variety of endogenous and exogenous substrates, Mrp1 plays important physiological roles in multiple tissues and also protects normal tissues against toxicants. However, the role of MRP1 in heart is largely unknown.
The role of Mrp1 in DOX-induced cardiotoxicity was investigated in Mrp1 null (Mrp1-/-) and their C57BL (WT) littermates. Chronic DOX caused body weight loss and hemotoxicity, and these adverse effects were significantly exacerbated in Mrp1-/- vs WT mice. Importantly, loss of Mrp1 potentiated DOX-induced cardiotoxicity, presenting as worsened cardiac function and more cellular apoptosis in DOX treated Mrp1-/- mice. Mrp1 also protected neonatal mouse cardiomyocytes (CM) and cardiac fibroblasts (CF) culture against DOX cytotoxicity in vitro. This was demonstrated by the decreased cell survival, more apoptosis and more DNA damage in DOX treated Mrp1-/- vs WT cells.
In addition, the effects of deletion of Mrp1 was studied on glutathione (GSH)/glutathione disulfide (GSSG) homeostasis, glutathione conjugate of 4-hydroxy-2-nonenal (GS-HNE) accumulation, protein oxidative damage and expression of antioxidant enzymes. Loss of Mrp1 led to significantly higher GSH and GSSG basal levels in heart. Following DOX treatment, Mrp1-/- CM and CF showed increased GSH and GSSG levels vs WT cells. Meanwhile, DOX increased expression of the GSH synthesis enzymes in Mrp1-/- but not WT cells. Thus, increased GSH synthesis may contribute to the further increase in the GSH pool in DOX-treated Mrp1-/- cells. DOX induced comparable increases of GS-HNE concentration in WT and Mrp1-/- mice hearts. Finally, expression of extracellular superoxide dismutase (ECSOD/SOD3) was significantly lower in Mrp1-/- vs. WT CM treated with either saline or DOX.
In summary, this study is the first to document a protective role of Mrp1 in DOX-induced cardiotoxicity. It gives critical information regarding the potential adverse sequelae of introduction of MRP1 inhibitors as adjuncts to clinical chemotherapy of multidrug resistant tumors.
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Σύνθεση και μελέτη πολυδύναμων συζευγμάτων φουλλερενίου C60 με δοξορουμπικίνηΜεσσάρη, Δανάη 25 May 2015 (has links)
Ο καρκίνος, αποτελεί στις μέρες μας μία από τις πιο συνήθεις ασθένειες καθότι προσβάλει ένα μεγάλο μέρος του παγκόσμιου πληθυσμού, ανεξαρτήτου ηλικίας και γι αυτό το λόγο, η θεραπεία του αποτελεί μία από τις μεγαλύτερες προκλήσεις της επιστημονικής κοινότητας. Η χορήγηση διαφόρων φαρμάκων έως τώρα, για την αντιμετώπισή του, έχει σαν αποτέλεσμα την προσβολή τόσο των καρκινικών, όσο και των υγειών κυττάρων. Κατά συνέπεια, προκαλούνται ποικίλες παρενέργειες στον ανθρώπινο οργανισμό, ορισμένες πολύ σοβαρές που δεν επιτρέπουν την χορήγηση θεραπευτικών δόσεων.
Η νανοτεχνολογία μπαίνει δυναμικά στη μάχη κατά του καρκίνου. Ο σχεδιασμός και η χρήση συστημάτων με μέγεθος στην νανοκλίμακα, προσφέρει νέους τρόπους για τον εντοπισμό, τη διάγνωση και τη θεραπεία του καρκίνου από τα πρώτα κιόλας στάδια και με ελάχιστες παρενέργειες. Τα νανοσωματίδια μακράς κυκλοφορίας (stealth nanoparticles) παρέχουν ένα νέο τρόπο χορήγησης των αντικαρκινικών φαρμάκων, λειτουργώντας ως φορείς που εξαγγειώνονται στην περιοχή του όγκου, επιτρέποντας με αυτόν τον τρόπο την εκλεκτική διάθεση του φαρμάκου που περιέχουν στα καρκινικά κύτταρα. Τα σωματίδια αυτά, έχουν την ικανότητα να τροποποιούνται κατάλληλα, ώστε να είναι βιοσυμβατά και να μπορούν να προσκολλούνται στα καρκινικά κύτταρα ή στο μικροπεριβάλλον τους, λειτουργώντας έτσι σαν φορείς στη στοχευμένη χορήγηση αντικαρκινικών φαρμάκων, μειώνοντας την τοξικότητα στους φυσιολογικούς ιστούς.
Οι νανοφορείς που έχουν μελετηθεί μέχρι σήμερα, εμφανίζουν σημαντικά προβλήματα, όπως δομική αστάθεια, δομική ετερογένεια και ελλειπή έλεγχο μεγέθους και σχήματος. Κατά συνέπεια, υπάρχει μία συνεχής ανάγκη ανάπτυξης νέων νανοφορέων ή βελτιστοποίηση των ήδη μελετημένων, προκειμένου να μπορούν να αξιοποιηθούν στην κλινική πράξη.
Τα φουλλερένια (C60), έχουν κινήσει το ενδιαφέρον των επιστημόνων σε πολλούς τομείς της έρευνας, συμπεριλαμβανομένου της θεραπείας κατά του καρκίνου. Η βιολογική τους σταθερότητα, το μικρό μέγεθος και η ικανότητα πρόσδεσης σε αυτά διαφόρων παραγόντων, όπως πολυμερή, βιοδραστικές ουσίες και μονάδες στόχευσης τα κατέστησε ικανά να λειτουργούν σαν νανοφορείς στη στοχευμένη χορήγηση φαρμάκων. Το μόνο τους μειονέκτημα είναι η μειωμένη διαλυτότητά τους στο νερό, το οποίο μπορεί να αντιμετωπιστεί με την πρόσδεση σε αυτά υδρόφιλων πολυμερών, όπως είναι η πολυαιθυλενογλυκόλη (PEG).
Στην παρούσα εργασία, παρουσιάζονται τα αποτελέσματα της σύνθεσης ενός συζεύγματος πεγκυλιωμένου μορίου φουλλερενίου (C60) με το αντικαρκινικό φάρμακο δοξορουμπικίνη, καθώς και η in vitro αξιολόγηση του τελικού προϊόντος. Στόχος είναι η αύξηση της αποτελεσματικότητας και η μείωση της τοξικότητας του φαρμάκου, μέσω στοχευμένης μεταφοράς στον καρκινικό όγκο. Ένα πεγκυλιωμένο σύζευγμα φουλλερενίου (C60) με δύο μόρια δοξορουμπικίνης (DOX2-C60-PEG, ένωση 4), συντέθηκε επιτυχώς και χαρακτηρίστηκε πλήρως μέσω 1H-NMR, 13C-NMR, IR, UV και TGA. Η δραστικότητα του τελικού προϊόντος, καθώς και ενός ήδη συντεθέντος συζεύγματος με ένα μόριο φαρμάκου DOX-C60-PEG (ένωση 2b), αλλά και του ενδιαμέσου συζεύγματος C60-PEG (ένωση 7) και της υδροχλωρικής δοξορουμπικίνης (DOX•HCl), ενάντια στον καρκίνο ελέγχθηκε in vitro σε καρκινικές σειρές κυττάρων μαστού MCF-7. Τα συζεύγματα DOX2-C60-PEG (4) και DOX-C60-PEG (2b) εμφάνισαν ικανοποιητική δράση αναστολής του πολλαπλασιασμού των κυττάρων, συγκρίσιμη με αυτήν του ελεύθερου φαρμάκου, ύστερα από σχετικά μακρό χρόνο επώασης. Μελέτη εντοπισμού της DOX χρησιμοποιώντας μικροσκοπία φθορισμού έδειξε ότι το φάρμακο στην περίπτωση των συζευγμάτων εντοπίζεται πολύ πιο αργά στο πυρήνα του κυττάρου, όπου και μπορεί να εξασκήσει φαρμακολογική του δράση, σε σύγκριση με την ελεύθερη DΟΧ. Αυτό σε συνδυασμό με την αργή απελευθέρωση του φαρμάκου από τα συζεύγματα, όπως έδειξαν πειράματα αποδέσμευσης σε προϊόν λύσης των MCF-7 καρκινικών κυττάρων, ερμηνεύει την συγκριτικά αργή εμφάνιση δράσης στην περίπτωση των συζευγμάτων.
Συμπερασματικά στην εργασία συντέθηκαν επιτυχώς φουλλερενικά συζεύγματα δοξορουμπικίνης τα οποία είχαν ικανοποιητική αντικαρκινική δραστικότητα έναντι καρκινικών κυττάρων ανθρώπινης καρκινικής σειράς. τα αποτελέσματα δικαιολογούν περαιτέρω μελέτες εφαρμογής του φουλλερενίου ως νανοφορέα για την χορήγηση τόσο δοξορουμπικίνης, όσο και άλλων φαρμάκων κατά του καρκίνου. / Until now, the administration of various drugs for its cure, affect both cancer and normal cells. Thus, many serious side effects are caused on the human body, which do not permit the administration of therapeutic doses of potent anticancer drugs.
Nanotechnology has entered dynamically”in the battle” against cancer. The design and the use of multifunctional nanoparticulte systems, provides new ways to detect, diagnose and treat cancer in the earliest stages and with minimal side effects. They can extravagate at tumor site, allowing direct drug access selectively to cancer cells. These particles have the capacity to be suitably modified in order to be biocompatible and can be attached to tumor cells or their microenvironment, acting as carriers in targeted delivery of anticancer drugs, reducing toxicity to normal tissues.
Drug nanocarriers explored to date, suffer from inherent limitations, including instability, structural heterogeneity and poor control over size and shape. Therefore, there is a continuing need to produce new or optimized, already studied nanocarriers, in order to render possible the use of such advanced nanomedicines in the clinic.
Fullerenes (C60), have attracted considerable interest in many fields of research, including the treatment of cancer. Because of their biological stability, their small size, and their ability to be suitably modified, attaching on them biological modifiers and drugs, they can be used as nanocarriers in targeted drug delivery. The main drawback of these carbon particles with regard to their biomedical applications, is their poor solubility to water. We can overcome this problem by attaching on fullerene particles hydrophilic polymers, such as polyethylene glycol (PEG).
In the present work, the results of the synthesis and the in vitro biological evaluation of a pegylated fullerene conjugate with the potent anticancer drug Doxorubicin are represented. The main goal is to increase efficacy and reduce toxicity of doxorubicin, through targeted delivery to tumors, by conjugating the drug to pegylated fullerenes. A pegylated fullerene-doxorubicin conjugate with two molecules of drug per fullerene particle (DOX2-C60-PEG, compound 4) has successfully been synthesized and was fully characterized by 1H-NMR, 13C-NMR, IR, UV and TGA. The anticancer activity of conjugates DOX2-C60-PEG (4), DOX-C60-PEG (compound 2b, with one DOX molecule per fullerene particle), and conjugate C60-PEG (control compound 7) and doxorubicin hydrochloride ((DOX•HCl), was evaluated in MCF-7 cancer cells lines. The fullerene-doxorubicin conjugates (2b, 4) exhibited satisfactory anticancer activity (inhibiting cancer cells proliferation), which became comparable to the activity of free drug at relatively long incubation times. In accordance with the relatively slow effect of DOX-C60-PEG conjugates on cells viability, DOX localization studies using fluorescence microscopy indicated that the drug is much more slowly localized in cell nucleus, where the drug can exert its pharmacological action, in the case of conjugates compared to free DOX.
In conclusion pegylated fullerene-doxorubicin conjugates were successfully synthesized. These DOX-C60-PEG conjugates exhibited comparable, but with a delayed onset, to free DOX anticancer activity against human cancer cell lines. The results obtained justify further investigation of the potential of these conjugates as anticancer nanomedicines.
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Συμμετοχή του πολυμορφισμού Ser326Cys του γονιδίου OGG1 στην κυτταρογενετική και κυτταροτοξική δράση της αντικαρκινικής ένωσης δοξορουβικίνης (Doxorubicin) σε καλλιέργειες ανθρώπινων λεμφοκυττάρων in vitroΠαναγίδης, Ανδρέας 22 October 2008 (has links)
Μελέτη της κυτταροτοξικής και κυτταρογενετικής δράσης της δοξορουβικίνης σε καλλιέργειες ανθρώπινων λεμφοκυττάρων in vitro, καθώς επίσης και της ικανότητας της εν λόγω ένωσης να επάγει την παραγωγή της 8-οξογουανίνης. Επίσης η μελέτη της συμμετοχής του πολυμορφισμού Ser326Cys στη δράση της παραπάνω ένωσης. / Evaluation of the involvment of Ser326Cys polymorphism to the cytotoxic and cytogenetic activity of doxorubicin in human lymphocytes cultured in vitro
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Fibroblast growth factor-2 protects neonatal rat cardiac myocytes from doxorubicin-induced damage via protein kinase C- dependent effects on efflux drug transportersWang, Jie 22 January 2013 (has links)
Introduction: Therapeutic agents like doxorubicin, an anthracycline antibiotic drug, are widely used in cancer chemotherapy. The use of doxorubicin is limited however by an increased risk of cardiac damage as a side effect, and an increased cancer cell drug resistance mediated by efflux drug transporters. Strategies are needed to protect the heart and still allow the benefits of drug treatment. “Basic” fibroblast growth factor-2 (FGF-2) is a multi-functional protein. It is angiogenic and cardioprotective against ischemia-reperfusion injury. FGF-2 can also regulate cancer cell drug resistance or sensitivity, however, so far, there is no evidence that FGF-2 protects against doxorubicin-induced cardiac damage through effects on efflux drug transporter levels or function.
Aims: To investigate whether: (1) FGF-2 can increase resistance to doxorubicin-induced neonatal rat cardiac myocyte damage; and if so whether (2) an effect on efflux drug transporters might contribute to this cardioprotection by FGF-2.
Methods: Neonatal rat cardiac myocyte cultures were treated with doxorubicin in the absence or presence of pre-treatment with FGF-2. To assess cell damage: (i) culture medium was tested for lactate dehydrogenase (LDH) activity as an indication of plasma membrane disruption; (ii) cells were stained with fluorescent apoptosis and necrosis biomarkers as well as (iii) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and acridine orange to assess DNA fragmentation or compaction. The role of FGF receptor (FGFR) or protein kinase C (PKC) was addressed through use of inhibitors including SU5402, or chelerythrine as well as bisindomaleimide. Multidrug resistance gene 1a and 1b (MDR1a, 1b), multidrug resistance gene 2 (MDR2) and multidrug resistance-related protein 1 (MRP1) gene expression, as well as the function of MDRs and MRPs protein products were assessed by real-time reverse transcriptase-polymerase chain reaction (qPCR), as well as retention/extrusion of (fluorescent) doxorubicin/calcein in cardiac myocytes, respectively. Efflux drug transporter inhibitors, including 20 µM cyclosporine A (CsA), 2 µM verapamil and 1 µM Tariquidar (XR9576) were used to asssess for a direct effect of FGF-2 on transporter function. Fluorescence-activated cell sorting (FACS) was used to measure fluorescent doxorubicin/calcein levels inside treated cardiac myocytes.
Results: Doxorubicin increased the incidence of programmed cell death, DNA damage, and lysosome and LDH activity, while decreasing cell number at 24 hours. FGF-2 prevented the detrimental effects of doxorubicin. In turn, the protective effects of FGF-2 were blocked in the presence of FGFR or PKC inhibitors. FGF-2 treatment significantly increased MDR1a, MDR1b, MDR2, MRP1 RNA levels by qPCR, and protein levels as assessed by function, and specifically extrusion of doxorubicin/calcein, in the presence of doxorubicin when compared to doxorubicin treatment alone. Furthermore, inhibition of efflux drug transporters with CsA and Tariquidar (XR9576) significantly reduced the ability of FGF-2 to protect against doxorubicin-induced damage; the beneficial effect of FGF-2 was completely blocked by pretreatment with verapamil.
Conclusion(s): These data indicate for the first time that exogenous FGF-2 can increase resistance to doxorubicin-induced neonatal rat cardiac myocyte damage, and implicate PKC and regulation of efflux transporter protein levels and/or function in the mechanism.
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Fibroblast growth factor-2 protects neonatal rat cardiac myocytes from doxorubicin-induced damage via protein kinase C- dependent effects on efflux drug transportersWang, Jie 22 January 2013 (has links)
Introduction: Therapeutic agents like doxorubicin, an anthracycline antibiotic drug, are widely used in cancer chemotherapy. The use of doxorubicin is limited however by an increased risk of cardiac damage as a side effect, and an increased cancer cell drug resistance mediated by efflux drug transporters. Strategies are needed to protect the heart and still allow the benefits of drug treatment. “Basic” fibroblast growth factor-2 (FGF-2) is a multi-functional protein. It is angiogenic and cardioprotective against ischemia-reperfusion injury. FGF-2 can also regulate cancer cell drug resistance or sensitivity, however, so far, there is no evidence that FGF-2 protects against doxorubicin-induced cardiac damage through effects on efflux drug transporter levels or function.
Aims: To investigate whether: (1) FGF-2 can increase resistance to doxorubicin-induced neonatal rat cardiac myocyte damage; and if so whether (2) an effect on efflux drug transporters might contribute to this cardioprotection by FGF-2.
Methods: Neonatal rat cardiac myocyte cultures were treated with doxorubicin in the absence or presence of pre-treatment with FGF-2. To assess cell damage: (i) culture medium was tested for lactate dehydrogenase (LDH) activity as an indication of plasma membrane disruption; (ii) cells were stained with fluorescent apoptosis and necrosis biomarkers as well as (iii) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and acridine orange to assess DNA fragmentation or compaction. The role of FGF receptor (FGFR) or protein kinase C (PKC) was addressed through use of inhibitors including SU5402, or chelerythrine as well as bisindomaleimide. Multidrug resistance gene 1a and 1b (MDR1a, 1b), multidrug resistance gene 2 (MDR2) and multidrug resistance-related protein 1 (MRP1) gene expression, as well as the function of MDRs and MRPs protein products were assessed by real-time reverse transcriptase-polymerase chain reaction (qPCR), as well as retention/extrusion of (fluorescent) doxorubicin/calcein in cardiac myocytes, respectively. Efflux drug transporter inhibitors, including 20 µM cyclosporine A (CsA), 2 µM verapamil and 1 µM Tariquidar (XR9576) were used to asssess for a direct effect of FGF-2 on transporter function. Fluorescence-activated cell sorting (FACS) was used to measure fluorescent doxorubicin/calcein levels inside treated cardiac myocytes.
Results: Doxorubicin increased the incidence of programmed cell death, DNA damage, and lysosome and LDH activity, while decreasing cell number at 24 hours. FGF-2 prevented the detrimental effects of doxorubicin. In turn, the protective effects of FGF-2 were blocked in the presence of FGFR or PKC inhibitors. FGF-2 treatment significantly increased MDR1a, MDR1b, MDR2, MRP1 RNA levels by qPCR, and protein levels as assessed by function, and specifically extrusion of doxorubicin/calcein, in the presence of doxorubicin when compared to doxorubicin treatment alone. Furthermore, inhibition of efflux drug transporters with CsA and Tariquidar (XR9576) significantly reduced the ability of FGF-2 to protect against doxorubicin-induced damage; the beneficial effect of FGF-2 was completely blocked by pretreatment with verapamil.
Conclusion(s): These data indicate for the first time that exogenous FGF-2 can increase resistance to doxorubicin-induced neonatal rat cardiac myocyte damage, and implicate PKC and regulation of efflux transporter protein levels and/or function in the mechanism.
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Clinical studies in aggressive non-Hodgkin's lymphoma with special reference to elderly patients /Ösby, Eva, January 2003 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.
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Therapeutic potential of rapamycin in renal parenchymal diseases insights from murine models of lupus nephritis, adriamycin nephropathy and renal ischemia reperfusion injury /Lui, Sing-leung. January 2008 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 263-321) Also available in print.
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High-frequency ultrasound drug delivery and cavitation /Diaz de la Rosa, Mario Alfonso, January 2007 (has links) (PDF)
Thesis (M.S.)--Brigham Young University. Dept. of Chemical Engineering, 2007. / Includes bibliographical references (p. 89-97).
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Influence of formulation parameters of Doxorubicin - poly(butyl cyanoacrylate) nanoparticles on the treatment of glioblastomas and evaluation of the body distribution of labelled nanoparticles in healthy and glioblastoma - bearing ratsAmbruosi, Alessandra. Unknown Date (has links)
University, Diss., 2006--Frankfurt (Main). / Zsfassung in dt. und engl. Sprache.
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Influência do extrato de chá verde na remodelação cardíaca induzida por administração de doxorrubicina /Modesto, Pamela Nayara. January 2015 (has links)
Orientador: Paula Schimidt Gaiolla / Coorientador: Elenize Jmas Pereira / Banca: Lisiane de Almeida Martins / Banca: Silméia Jamas Cazan / Resumo: A doxorrubicina (DOX) é um medicamento amplamente utilizado como agente quimioterápico, tendo eficácia no tratamento de inúmeros tipos de cânceres. Entretanto, o uso desse medicamento pode proporcionar efeitos indesejáveis, como a cardiotoxidade. Diferentes mecanismos têm sido propostos para a cardiotoxicidade induzida pela doxorrubicina, como o estresse oxidativo, inflamação e alterações da matriz extracelular, levando ao processo de remodelação cardíaca. Chá verde (Camellia sinensis), uma das bebidas mais populares em todo o mundo, tem demonstrado uma relação positiva entre o seu consumo habitual e a proteção contra doenças cardiovasculares e contra alguns tipos de neoplasias. Isso se deve as propriedades antioxidantes, antiinflamatórias, antiapoptóticas encontradas nas catequinas, presentes no chá verde. Portanto, é possível que o mesmo atenue os afeitos cardiotóxicos da doxorrubicina, retardando o processo de remodelação cardíaca. O objetivo do presente estudo foi avaliar se o extrato de chá verde atenua a remodelação cardíaca induzida pela doxorrubicina, por meio da avaliação de variáveis bioquímicas, celulares, intersticiais e variáveis morfofuncionais cardíacas. Para isso, foram utilizados ratos Wistar machos com peso de 300 á 350 gramas. Esses animais foram divididos em 4 grupos: CP (controle) que receberam ração padrão e administração intraperitoneal de solução salina, CCV (controle + chá verde) que receberam ração adicionada de extrato de chá verde e administração intraperitoneal de solução salina, DX (doxorrubicina) que receberam ração padrão e administração intraperitoneal de doxorrubicina e DX-CV (doxorrubicina + chá verde) que receberam ração adicionada de extrato de chá verde e administração intraperitoneal de doxorrubicina. A ração foi ofertada por 35 dias e no 33◦ dia foi feita a infusão de doxorrubicina ou de solução salina foram na mesma proporção... / Abstract: Doxorubicin (DOX) is a widely used drug as a chemotherapeutic agent having efficacy in the treatment of numerous cancers. However, use of this drug may provide undesirable effects such as cardiotoxicity. Various mechanisms have been proposed for doxorubicin cardiotoxicity, such as oxidative stress, inflammation and alterations in the extracellular matrix, leading to cardiac remodeling. Green tea (Camellia sinensis), the most popular drinks in the world, has demonstrated a positive relationship between regular consumption and protection against cardiovascular disease and some types of cancer. This is the antioxidant, anti-inflammatory, antiapoptotic found in catechins present in green tea. It is therefore possible that it mitigates the cardiotoxic fond of doxorubicin, slowing the process of cardiac remodeling. The aim of this study was to evaluate whether the green tea extract attenuates cardiac remodeling induced by doxorubicin, through the evaluation of biochemical variables, cell phones, and interstitial cardiac morphofunctional variables. For this, was used male Wistar rats weighing 250 to 300 grams. These animals were divided into 4 groups: CP (control) received standard chow and intraperitoneal administration of saline, CCV (control + green tea) receiving feed added green tea extract and intraperitoneal administration of saline, DX (Doxorubicin) who received standard chow and intraperitoneal administration of doxorubicin and DX-CV (doxorubicin + green tea) fed diets with added green tea extract and intraperitoneal administration of doxorubicin. The feed was supplied for 35 days and on day 33◦ doxorubicin or infusion of saline solution were carried out in the same ratio (20 mg / kg single dose) and the animals were euthanized 48 hours after drug injection. The rats were subjected to the echocardiography before and 48 hours after injection of doxorubicin. Was conducted evaluation of oxidative stress by spectrophotometry ... / Mestre
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