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阿霉素(ADM)属于蒽环类抗生素,用它治疗一系列实体瘤(乳腺癌、肺癌、卵巢癌、膀胱癌、甲状腺癌、软组织肉瘤、原发性肝癌等),也用于治疗某些血组织增生病(急性白血病、淋巴肉芽肿瘤)。ADM毒性表现为抑制造血功能(白细胞与淋巴细胞减少),以及脱发、恶心、呕吐、口腔炎,但这些副作用具有可逆性,一旦停药后症状即可消失。但是ADM正如蒽环类中其它抗肿瘤抗生素一样也具有心脏毒性作用,有时引起心肌病和郁血性心功能不全。ADM因治疗许多恶性肿瘤被广泛地应用,所以及早诊断、预防和治疗这类抗生素所引起的心肌中毒是一个迫切问题。文献报道在阿霉素心肌毒性的一些风险因子中,主要风险因子是体内ADM总蓄积 相似文献
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近年阿霉素(ADM)应用治疗肿瘤的效果报道不少,但它的剧作用尤其是对心脏毒性作用构成了限制其应用的重要因素。现将我院应用阿霉素为主联合治疗肿瘤患者病例加以分析如下。1资料与方法:收集我院经阿霉素为联合方案化疗的患者共93例,其中男57例,女36例;平均年龄55.6岁;部位肿瘤以支气管肺癌76例,其它肿瘤17例。全部病例均经病理确诊,并首次接受化疗的患者。全部病例用ADM为主的联合化疗,经静脉全身化疗,用药3周为一疗程。ADM用量30~6O0ms之间,<100mg(1~2疗程)40例,tol00mg(3疗程以上)53例。心脏毒性监测以用日产65… 相似文献
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阿霉素联合治疗恶性肿瘤150例对心脏毒性的临床观察 总被引:1,自引:0,他引:1
阿霉素联合治疗恶性肿瘤150例对心脏毒性的临床观察福建省肿瘤医院吴国森,林传荣福建省立医院柯文沅阿霉素是常用的广谱抗肿瘤抗生素,动物试验和临床应用均表明其对心脏有一定的毒性,现总结近五年来应用以ADM为主的联合化疗方案治疗恶性肿瘤150例,对其心脏的... 相似文献
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维生素C防治阿霉素对心脏毒性的临床对比研究 总被引:1,自引:0,他引:1
本文对30例恶性肿瘤病人接受鲩滨阿霉素化疗期间着重观察维生素C防治阿霉素对心脏的毒性反应,设维生素C组14例,化疗前3天开始口服维生素C0.5tid直至化疗结束;对照组16例不服维生素C。 相似文献
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阿霉素 (ADM)是蒽环族抗肿瘤抗生素 ,具有广谱抗肿瘤作用 ,广泛应用于临床中 ,但由于 A DM具有心脏毒性 ,故在临床应用中受到一定限制 [1 ]。我们将 1997年 2月至2 0 0 0年 2月用 ADM治疗资料较完整的 70例乳腺癌进行总结。1 资料与方法1.1 临床资料 :70例乳腺癌均为女性 ,年龄 30~ 6 9岁。其中单纯癌 31例 ,浸润性导管癌 2 0例 ,黏液腺癌 12例 ,髓样癌 5例 ,硬癌 2例。按 TN M国际分期 : 期 16例 , 期 34例 , 期 2 0例。1.2 方法 :全部病例治疗前后均检测心电图 ,并进行血象 ,肝、肾功能及影像学检查。治疗采用 CAF方案 :CTX6 … 相似文献
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目的:研究硫普罗宁(MPG)对阿霉素(ADM)心脏毒性的保护作用及机制。方法:建立ADM损伤大鼠心脏模型,灌胃给予MPG,检测血清肌钙蛋白工(cTnⅠ)、肌酸激酶同工酶(CK—MB)及脑钠肽(BNP)、心肌组织超氧化物歧化酶(SOD)活力,丙二醛(MDA)、一氧化氮(NO)含量及一氧化氮合酶(NOS)的活性,并观察心肌组织病理改变。结果:与ADM大鼠心脏模型组相比,MPG干预ADM处理后大鼠的血清cTnI、CK.MB及BNP显著降低(P〈0.05或P〈0.01),心肌组织SOD活力显著增高,MDA、NO含量,总NOS活力及iNOS活力显著降低(P均〈0.01),心肌组织病理积分显著下降(P〈0.05)。结论:MPG对ADM心脏毒性具有较好的保护作用;MPG可能通过恢复心肌组织SOD的活力、抑制iNOS活性使心肌组织NO产生减少,从而减轻ADM所致大鼠心肌组织的氧化损伤。 相似文献
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Tomonari M To H Nishida M Mishima T Sasaki H Kurose H 《Journal of pharmacological sciences》2011,115(3):336-345
We revealed that pre-treatment with docetaxel (DOC) 12 h before adriamycin (ADR) administration significantly reduced ADR-induced toxic death compared with the simultaneous dosing schedule that was commonly used in previous studies. We considered that pre-treatment with DOC relieves ADR-induced cardiotoxicity. In this study, we investigated the influence of DOC on the pharmacokinetics and pharmacodynamics of ADR in order to clarify the mechanism by which DOC pre-treatment relieves ADR-induced cardiotoxicity. When ADR and/or DOC was intravenously administered, the DOC pre-treatment (DOC-ADR) group showed significantly less toxic death than the ADR-alone group. We examined hepatopathy, nephropathy, leukopenia, and cardiotoxicity, all of which can cause toxic death. Of these toxicities, ADR-induced cardiotoxicity was significantly relieved in the DOC-ADR group. To elucidate the mechanism by which DOC pre-treatment relieved ADR-induced cardiotoxicity, lipid peroxidation as a proxy for the free radical level and the pharmacokinetics of ADR were measured. There was no difference in the pharmacokinetics of ADR between the ADR and DOC-ADR groups. On the other hand, the DOC-ADR group showed significantly inhibited lipid peroxidation in the heart compared with the ADR group. It was considered that DOC pre-administration inhibited ADR-induced free radicals and decreased cardiotoxicity. 相似文献
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Selcoki Y Uz E Bayrak R Sahin S Kaya A Uz B Karanfil A Ozkara A Akcay A 《Toxicology》2007,239(1-2):53-59
Cyclosporine A (CsA) is a frequently used immunosuppressive agent in transplant medicine to prevent rejection and in the treatment of autoimmune diseases. However, CsA generates reactive oxygen species, which causes nephrotoxicity, hepatotoxicity and cardiotoxicity. The use of antioxidants reduces the adverse effects of CsA. The aim of this study is to determine the protective effects of erdosteine on CsA-induced heart injury through tissue oxidant/antioxidant parameters and light microscopic evaluation in rats. CsA cardiotoxicity was induced by administrating an oral dose of 15mg/kg CsA daily for 21 days. The rats were divided into four groups: control group (n=4), CsA administrated group (15mg/kg, n=5), CsA+erdosteine administrated group (10mg/kg day orally erdosteine, n=4) and only erdosteine administrated group (10mg/kg day orally n=5). CsA treated rats showed increase in the number of infiltrated cells and disorganization of myocardial fibers with interstitial fibrosis. The number of infiltrated cells, disorganization of myocardial fibers and interstitial fibrosis was diminished in the hearts of CsA-treated rats given erdosteine. The malondialdehyde, the protein carbonyl content and nitric oxide levels were increased in the cyclosporine A group in comparison with the control and CsA plus erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in CsA plus erdosteine group than CsA group. However, the CAT, GSH-Px and SOD activities were significantly lower in CsA group than in control group and erdosteine group. These results suggest that erdosteine has protective effect against CsA-induced cardiotoxicity. 相似文献
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阿霉素致大鼠心脏氧化损伤及其机制的研究 总被引:11,自引:0,他引:11
目的观察不同剂量阿霉素(ADR)给药后不同时间对大鼠心脏的作用,探讨ADR心脏毒性损伤的可能作用机制。方法60只大鼠随机分为对照组和3个给药组。给药组分别单次腹腔注射5、10和20ms/kg的ADR溶液;对照组给予生理盐水。给药后第1、2和4天每组分别处死5只动物,取心室制备组织匀浆,用硫代巴比妥酸法(TBA)测定丙二醛(MDA)含量,二硫代双硝基苯甲酸法(DTNB)测定总巯基(TSH)和非蛋白巯基(NPSH)含量,Griess试剂法测定一氧化氮(NO)含量。结果随着剂量的增加,给药后第1天心脏组织中NPSH、TSH含量增加;给药后第2天TSH、NO含量增加;给药后第4天MDA、NO含量增加,NPSH含量降低;与对照组比较,20ms/kg组差异有显著性(P〈0.05,P〈0.01)。结论阿霉素致心脏损伤的机制可能与心脏组织中NPSH的耗竭及NO产生过多有关。 相似文献
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Nagla A. El-Shitany Sahar El-Haggar Karema El-desoky 《Food and chemical toxicology》2008,46(7):2422-2428
Adriamycin is a potent anticancer agent, its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study aimed to investigate the possible protective role of the natural antioxidant silymarin on ADR-induced heart and kidney toxicity. Studies were performed on four groups of rats. 1--control group, 2--silymarin group (50 mg/kg), 3--adriamycin group (10 mg/kg), 4--adriamycin+silymarin group. On the third day after ADR injection, plasma was separated for determination of LDH, CPK, cholesterol and total lipids. 30 days after ADR injection, plasma was separated for determination of creatinine and urea levels. Frozen heart specimens (72 h) and frozen kidney specimens (30days) were used for estimation of lipid peroxides and GSH contents. Histopathological examinations of heart and kidney sections were also done. Pretreatment of ADR-treated rats with silymarin resulted in a significant decrease in the plasma CPK, LDH, creatinine and urea. On the other hand silymarin pretreatment did not change ADR-induced hyperlipidemia. Silymarin pretreatment significantly decreased the myocardial MDA contents. In addition, silymarin pretreatment normalized renal tissue contents of MDA and GSH. Histopathological examination of heart and kidney sections revealed that ADR caused only mild myocardial injury in silymarin pretreated rats. Also, silymarin pretreatment inhibited ADR-induced renal tubular damage in rats. These results have suggested that, silymarin ameliorated ADR-induced cardiotoxicity and protected against ADR-induced nephrotoxicity in male albino rats. The mechanisms of silymarin induced protection against ADR-induced toxicities were proved to be due to inhibition of lipid peroxidation and protection against GSH depletion. 相似文献
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Arunachalam S Kim SY Lee SH Lee YH Kim MS Yun BS Yi HK Hwang PH 《Journal of natural medicines》2012,66(1):149-157
Adriamycin (ADR) is a potent anticancer drug. Its clinical applications are limited due to its cardiotoxicity. Oxidative stress
is responsible for cardiomyopathy induced by ADR. Previous studies have demonstrated that davallialactone (DAVA), extracted
from mushroom Inonotus xeranticus, has potential antiplatelet aggregation activity and free radical scavenging properties. In this study, we investigated whether
DAVA has protective effects against ADR-induced free radical accumulation and apoptosis in cardiac muscle cells and compared
the effects of DAVA with N-acetylcysteine, a potent antioxidant. We evaluated the effect of DAVA on ADR-induced cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) assay and crystal violet staining, the reactive oxygen species (ROS) production by flow cytometry, and the expression
of stress-related proteins like Cu/Zn superoxide dismutase (SOD), Mn-SOD, and the involvement of mitogen-activated protein
kinase pathway by Western blot analysis. Apoptosis was assessed by nuclear condensation and the expression levels of pro-apoptotic
proteins, such as caspase-3 and polyadenosine diphosphate-ribose polymerase (PARP). The cardio-protective effects of DAVA
were also evaluated in an in vivo study in an animal model of ADR-induced acute cardiomyopathy. Our results showed that DAVA
significantly increased the viability of doxorubicin-injured H9c2 cells and inhibited ADR-induced ROS production, apoptosis,
and the expression of Cu/Zn SOD and Mn-SOD. DAVA also inhibited the expression of extracellular signal-regulated kinase (ERK)
and c-Jun N-terminal kinase (JNK), which was activated by ADR. In the in vivo animal model, treatment involving DAVA significantly
reduced cardiomyocyte lesions. These results suggest that DAVA is a potentially protective agent for ADR-induced cardiotoxicity
in cardiomyocytes and can be a potential candidate to protect against cardiotoxicity in ADR-treated cancer patients. 相似文献
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Cyclosporine A (CsA) is the immunosuppressor, which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been considered as one of the possible mechanisms of CsA-induced cardiotoxicity. The present investigation examines the ability of caffeic acid phenethyl ester (CAPE), which is an active component of propolis extracts, as a natural antioxidant to protect against CsA-induced oxidative stress and cardiotoxicity. CsA cardiotoxicity was induced by subcutaneous injection of CsA at a dose of 15 mg/kg/body weight daily for 21 days in rats. Cardiotoxicity was evaluated by morphological and biochemical studies. CsA treated rats showed degenerative changes with cardiac fibrosis localized around the fibers. These latters were disorganised and the network was disappeared. The ROS production was increased whereas cytochrome-c-oxidase decreased. The expression and levels of matrix metalloproteinase 2 (MMP2) were increased whereas those of its inhibitor were downregulated. CAPE subcutaneous administration (15 micromol/kg/day) improved cardiac cytoarchitecture, decreased the levels and the expression of MMP2, and increased those of TIMP2 proteins. Moreover, it increased cytochrome-c-oxidase activity and decreased ROS production. These results suggest that CAPE could have protective effect against CsA-induced cardiotoxicity. 相似文献
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The therapeutic usefulness of doxorubicin (DXR), an anthracycline antibiotic, is limited by its cardiotoxicity. The present study investigated the effects of telmisartan, an angiotensin II receptor (AT1) antagonist against doxorubicin-induced cardiotoxicity in rats using biochemical and histopathological approaches. Doxorubicin (20 mg/kg) was injected intraperitoneally (ip) as a single dose and telmisartan (10 mg/kg) was administered orally for 7 days. Rats treated with DXR showed cardiotoxicity as evidenced by elevation of serum lactate dehydrogenase (LDH) activity, tissue malondialdehyde (MDA) level, catalase activity and a decrease in the level of glutathione (GSH). Pre- and post-treatment with telmisartan elicited a significant decrease in the activities of LDH and catalase in comparison with DXR-treated group. Furthermore, pretreatment with telmisartan also decreased lipid peroxidation (MDA level) and increased the GSH content in comparison with DXR group. However, the difference in lipid peroxidation and GSH content were not statistically significant in post-treated group. Histopathological studies showed disruption of cardiac tisuues in DXR groups. Pre- and post-treatment with telmisartan reduced the damage of cardiac tissue in rats. These results suggest that telmisartan treatment provides a significant protective effect against acute-doxorubicin induced cardiotoxicity in rats. 相似文献
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观察槲皮素对阿霉素致小鼠心肌损伤的保护作用并初步探讨其机制。腹腔注射阿霉素(20 mg·kg-1)复制小鼠心肌损伤模型,检测心电图、心肌超微结构,血清NO含量和iNOS活性,心肌组织LDH、SOD、MDA的水平和p53蛋白表达。并观察槲皮素(50,100及200 mg·kg-1)对上述指标的影响。阿霉素可导致小鼠心律失常和心肌超微结构损伤;使NO、iNOS、MDA和LDH的水平升高,SOD的水平降低;p53蛋白表达增强。槲皮素(50,100及200 mg·kg-1)可拮抗阿霉素所致的上述变化。槲皮素对阿霉素性小鼠心肌损伤具有保护作用,其机制与增强SOD活力、降低iNOS活性、抑制p53蛋白表达等有关。 相似文献
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目的:探讨磷酸肌酸钠对小鼠阿霉素心肌损伤的保护作用。方法:雌性BALB/C小鼠60只,建立阿霉素心肌病模型,随机分为磷酸肌酸钠组、阿霉素组、正常对照组。观察小鼠的一般情况,血清中心肌酶TnI、N端前脑钠肽(NT-proB-NP)及心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、ATP酶及乳酸脱氢酶(LDH)的变化,心肌组织HE染色病理变化。结果:与阿霉素组比较,磷酸肌酸钠组LDH、MDA明显降低(P<0.05),SOD和ATP酶活力明显升高(P<0.05);血清NT-proBNP及TnI水平降低(P>0.05)。阿霉素组心肌组织出现明显的水肿、变性。结论:磷酸肌酸钠通过减少氧自由基对阿霉素所致的心肌损伤具有保护作用。 相似文献
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Kelishomi RB Ejtemaeemehr S Tavangar SM Rahimian R Mobarakeh JI Dehpour AR 《Toxicology》2008,243(1-2):96-104
Doxorubicin (DOX) is an anthracycline antibiotic that is widely used as a chemotherapeutic agent. However, usefulness of this agent is limited due to its cardiotoxic effects. The aim of this study was to investigate the potential protective effects of morphine against DOX-induced cardiotoxicity in rats. Male Sprague-Dawley rats were treated with morphine (10mg/kg i.p.) and/or DOX (1.25mg/kg i.p.), 4 times per week, for 4 weeks. Mortality, general condition and body weight of the animals were observed during the whole treatment, and for a further 4-week period, until the end of experiment. Evaluation of cardioprotective efficacy of morphine was performed by analyzing the electrocardiographic parameters and contractility force of left ventricular papillary muscle. Necropsy was also performed at the end of the experiment, and heart excision, weight and macroscopic examination were done before histological evaluation. Doxorubicin caused heart disturbances manifested by prominent electrocardiographic changes (S(alpha)-T prolongation), decrease of the heart contractility, as well as histopathologically verified myocardial lesions. The changes in heart parameters were accompanied by 50% mortality rate, significant decline in body mass and severe effusion intensity score of the animals. Application of morphine before each dose of DOX either significantly reduced or completely prevented its toxic effects. Therefore, since morphine had very good protective effects against a high dose of DOX given as a multiple, low, unitary dose regimen, not only on the heart but on the whole rat as well, it could be recommended for further investigation in this potentially new indication for clinical application. 相似文献