Interaction of doxorubicin and idarubicin with red blood cells from acute myeloid leukaemia patients

Marczak, Agnieszka; Kowalczyk, Aleksandra; Wrzesień‐Kuś, Agata; Robak, Tadeusz; Jóźwiak, Zofia

doi:10.1016/j.cellbi.2005.09.001

Cited by 24 publications

(21 citation statements)

References 40 publications

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“…As shown in Figure 7D and E, there was no evident body weight loss for each group during the treatment, while only iRGD-SSL-DOX group exhibited a similar level of body weight change without tumor (the percentage change of body weight compared to weight before treatment) with control group, indicating better toleration. Previous results claimed myelotoxicity (Morelli et al, 1997) and damage to erythrocytes and hemoglobin (Marczak et al, 2006) caused by DOX treatment. Here, different from free DOX and SSL-DOX, iRGD-SSL-DOX could not significantly change hemoglobin (HGB) levels during the treatment ( Figure 7F).…”

Section: Tumor Growth Inhibition Studymentioning

confidence: 99%

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

et al. 2014

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(2015) A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma, Drug Delivery, 22:1, 10-20, DOI: 10.3109/10717544.2014 Here, iRGD-modified and doxorubicin-loaded sterically stabilized liposomes (iRGD-SSL-DOX) and passive liposomes (SSL-DOX) were prepared. A series of experiments were performed to evaluate the tissue penetration, cell penetration, tumor blood vessel damage and anti-tumor effect. The results of flow cytometry and confocal microscopy studies showed that iRGD-SSL-DOX with 5% DSPE-PEG 2000 -iRGD achieved higher cellular uptake level than that of SSL-DOX on B16 melanoma cells. iRGD-SSL-DOX also exhibited stronger cell growth inhibition in cytotoxicity experiments. The tumor penetrating effect of iRGD was further confirmed by imaging and cellular uptake studies in vivo, in which higher distribution of iRGD-modified liposomes in tumor tissue and tumor cells was observed. Moreover, iRGD-SSL-DOX displayed improved tumor growth inhibition and anti-angiogenesis with less systemic toxicity in an armpit B16 melanoma model. In conclusion, iRGD reserved its tumor-penetrating properties well when modified on the surface of liposomes at optimal density and iRGD-SSL-DOX would be a promising drug delivery system for active targeting tumor therapy.

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Section: Tumor Growth Inhibition Studymentioning

confidence: 99%

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

et al. 2014

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“…Briefly, EPR identifies changes in the spin tropic movement of an unpaired electron. As a spin label, we used 5-doxylstearic acid (5-DSA), which is a derivative of stearic acid with a nitroxyl free radical group located at the fifth carbon, to determine the local fluidity near the polar head groups of the lipid bilayer (Marczak et al 2006). The final concentration of 5-DSA was 1 mM in a 20 ml suspension of INS-1E cells.…”

Section: Plasma Membrane Fluidity Analysis By Electron Paramagnetic Rmentioning

confidence: 99%

Distinct pathways of cholesterol biosynthesis impact on insulin secretion

Zuniga-Hertz

Rebelato

Kassan

et al. 2014

Journal of Endocrinology

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Results from previous investigations have indicated that glucose-stimulated insulin secretion (GSIS) is affected by changes in cholesterol and its intermediates, but the precise link between secretion and cholesterol has not been thoroughly investigated. In this study, we show the contribution of both protein isoprenylation and cholesterol-dependent plasma membrane structural integrity to insulin secretion in INS-1E cells and mouse islets. Acute (2 h) inhibition of hydroxyl-methylglutaryl-CoA reductase by simvastatin (SIM) resulted in inhibition of GSIS without reduction in total cellular cholesterol content. This effect was prevented by cell loading with the isoprenyl molecule geranylgeranyl pyrophosphate. Chronic (24 h) inhibition of cholesterol biosynthesis resulted in inhibition of GSIS with a significant reduction in total cellular cholesterol content, which was also observed after the inhibition of cholesterol biosynthesis downstream of isoprenoid formation. Electron paramagnetic resonance analyses of INS-1E cells showed that the SIM-induced reduction in cholesterol increased plasma membrane fluidity. Thus, the blockade of cholesterol biosynthesis resulted in the reduction of availability of isoprenoids, followed by a reduction in the total cholesterol content associated with an increase in plasma membrane fluidity. Herein, we show the different contributions of cholesterol biosynthesis to GSIS, and propose that isoprenoid molecules and cholesterol-dependent signaling are dual regulators of proper b-cell function.

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“…In contrast, increased serum iron level in mice was recorded 3 d after treatment with a single dose of doxorubicin (0.25 mg, intraperitoneal) and then rebounded to normal value after 6 d due to the clearance of the doxorubicin-iron complexes by the liver and/or kidney (Bartnikas et al, 2011). The reduced blood hemoglobin concentration was attributed to several parameters indicative of red blood cell function and integrity and have been shown to be negatively affected by anthracyclines, namely (1) interaction of some fractions of doxorubicin and its metabolites with hemoglobin (Misiti et al, 2003), (2) interaction of doxorubicin with the membrane components of erythrocytes causes changes in the fluidity of the hydrophobic parts of the lipid bilayer and erythrocyte membrane protein conformation, resulting in enhancing the erythrocyte membrane lipid peroxidation and increasing the osmotic fragility of the red blood cells (Marczak et al, 2006). Doxorubicin cardiotoxicity has been shown to be inextricably linked to the accumulation of free ionic iron in the heart tissue accompanied by a reduction in serum iron (Kwok & Richardson, 2002;Rajagopalan et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Aloin: A natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities

Esmat

Said

Khalil

2014

Pharmaceutical Biology

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Context: The antitumor activity of aloin, the active anthraquinone of Aloe juice, against different murine and human tumors has been reported. Objective: In the present study, the impact of repeated aloin treatment at its maximum tolerated dose on serum levels of lipid profile, some elements, iron status and kidney function, compared with doxorubicin (a cardiotoxic anthracycline and inhibitor of erythropoiesis), was assessed. Materials and methods: Rats were treated with a single dose of doxorubicin (30 mg/kg body weight, intraperitoneal) or aloin (50 mg/kg body weight, intramuscular) twice weekly over 2 weeks. Results: Acute doxorubicin treatment elevated serum levels of triacylglycerols (59.90%), total cholesterol (42.29%), cholesteryl esters (54.75%), low density lipoprotein-cholesterol (230.16%), very low density lipoprotein-cholesterol (56.42%), urea (287.53%), and creatinine (85.38%), whereas serum high density lipoprotein-cholesterol, sodium, and calcium levels were reduced (44.61, 9.61, and 9.76%, respectively), as compared with controls. In contrast, aloin treatment showed insignificant changes in all the aforementioned parameters. Both doxorubicin and aloin induced erythropoiesis impairment demonstrated by a reduction in blood hemoglobin concentration. While aloin treatment elevated serum iron level (30.28%), doxorubicin treatment reduced serum levels of iron (51.47%) and percent transferrin saturation (55.21%), and in contrast, increased serum total iron binding capacity (34.85%). The chelating affinities of iron-aloin and -doxorubicin complexes, which contain bidentate iron-binding moieties, have been shown in the infrared spectra. Discussion and conclusion: The non-cardiotoxic effect of aloin treatment was due to its non-atherogenic and iron-chelating activities, which might also contribute in part to its anti-proliferative activity.

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Interaction of doxorubicin and idarubicin with red blood cells from acute myeloid leukaemia patients

Cited by 24 publications

References 40 publications

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

Distinct pathways of cholesterol biosynthesis impact on insulin secretion

Aloin: A natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities

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