Doxorubicin Toxicity

Manalo, Felipe B.

doi:10.1001/jama.1975.03260010058025

Cited by 16 publications

(5 citation statements)

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“…Doxorubicin (DOX) is an effective antineoplastic agent that is used to treat a wide spectrum of human malignancies and remains one of the most commonly prescribed drugs (Pautier et al 2015 ; Tap et al 2016 ). However, its clinical usage is limited by the development of severe dose-dependent acute and chronic cardiomyopathy (Manalo et al 1975 ; Carvalho et al 2014 ), which is usually refractory to common medications. Approximately 10% of patients treated with DOX will develop cardiomyopathy (Lipshultz et al 2010 ).The pathogenic mechanisms responsible for DOX-induced cardiotoxicity have not been completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

Scutellarin protects against doxorubicin-induced acute cardiotoxicity and regulates its accumulation in the heart

et al. 2017

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The clinical use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. The present study investigated the effects of scutellarin against DOX-induced cardiotoxicity in rats using pharmacodynamic and pharmacokinetic approaches. DOX (20 mg/kg) was injected intraperitoneally (i.p.) as a single dose, and scutellarin (5 mg/kg/day) was injected intravenously (i.v.) for 3 days. Rats treated with DOX showed acute cardiotoxicity as indicated by the elevated serum lactate dehydrogenase (LDH) activity (4057.8 ± 107.2 vs. 2032.7 ± 70.95), tissue malondialdehyde (MDA) level (2.083 ± 0.10 vs. 1.103 ± 0.09), cardiac troponin T (cTnT) concentration (0.1695 ± 0.0114 ng/mL), the decreased left ventricular ejection fraction (LVEF) (47.75 ± 15.79 vs. 78.72 ± 7.25) and left ventricular fractional shortening (LVFS) (20.66 ± 8.06 vs. 43.7 ± 6.76) compared with those of the control group. Cotreatment with scutellarin significantly decreased the LDH activity (2595.9 ± 72.73), MDA level (1.380 ± 0.06), cTnT concentration (0.0222 ± 0.0041 ng/m L), increased LVEF (76.70 ± 3.91) and LVFS (40.28 ± 3.68). Histopathological studies showed disruption of cardiac tissues in the DOX groups. Cotreatment with scutellarin reduced the damage to cardiac tissues. In the pharmacokinetic and tissue distribution study, scutellarin reduced the heart tissue exposure to DOX but did not change the AUC of plasma. These results suggest that scutellarin can protect against DOX-induced acute cardiotoxicity through its antioxidant activity and alterations of heart concentrations.

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Section: Introductionmentioning

confidence: 99%

Scutellarin protects against doxorubicin-induced acute cardiotoxicity and regulates its accumulation in the heart

et al. 2017

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“…Despite its efficacy in cancer, its clinical usage is limited because of serious side effects such as cardiac toxicity, skin toxicity and blood problems. 27,28 Therefore, FA-SNs were used as a DOX carrier for the purpose of enhancing its therapeutic index and decreasing its toxic effects.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects

Gao

Liu

et al. 2012

Nanoscale

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Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.

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“…The stability and high configurational flexibility of SNA structures position them as an innovative drug delivery platform, attracting significant attention in the field of combined cancer therapy. SNA structures prevent the strong toxicity and poor targeting of Dox, [83][84][85] endowing them with unique cellular uptake capabilities and controlled drug delivery. Liang developed pH-responsive Dox-SNA conjugates, facilitating the delivery of Dox to cancer cells and pH-dependent drug release (Fig.…”

Section: Snas With Therapeutic Drugsmentioning

confidence: 99%