Nucleolar Organizer Regions in Cardiac Lesions Induced by Doxorubicin

Leblanc, Bernard; Mompon, P.; Espérandieu, Odile; Geffray, B.; Guillermo, Christine

doi:10.1177/019262339101900213

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…Reductions in cardiac total protein, RNA, and DNA concentrations following doxorubicin treatment were associated with sharp elevations in protein/DNA and RNA/DNA ratios (Table ) and are mainly due to the enhanced oxidative stress leading to membrane lipid peroxidation, excess free radical generation, mitochondrial dysfunction, and depletion of antioxidant defense mechanisms. The increased rate of RNA and protein synthesis as reflected in the increased RNA/DNA and protein/DNA reflect an exacerbated demand of the myocardial cells for proteins as previously reported [Rajagopalan et al., ; Leblanc et al., ].…”

Section: Discussionsupporting

confidence: 63%

In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

Esmat

Said

Hamdy

et al. 2012

Drug Development Research

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Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV In the present study, the cardiotoxicity of aloin, a naturally occurring anthraquinone glycoside with antiproliferative activity was compared with doxorubicin, a cardiotoxic anthracyline drug, in rats. The antioxidant and iron‐chelating activities of aloin and doxorubicin in vitro were also evaluated. Rats treated with aloin (50 mg/kg body weight, intramuscular)) twice weekly over 2 weeks showed no signs of cardiotoxicity as assessed by an absence of changes in relative heart weight, serum level of heart function enzymes, and a lack of degeneration in the myocardium of the left ventricle. Acute doxorubicin administration (30 mg/kg body weight, intraperitoneal) to rats produced severe cardiotoxicity as supported by biochemical and histological studies. Aloin did not induce oxidative stress or enhance the endogenous antioxidant defense system in the heart. In vitro antioxidant tests showed that aloin, in contrast to doxorubicin, had substantial antioxidant activity represented by scavenging of 1,1‐diphenyl 2‐picrylhydrazyl and nitric oxide· radicals, inhibition of lipid peroxidation, and ferric‐reducing antioxidant activity in addition to iron chelating potential. Ventricular inducible nitric oxide synthase protein expression was unaffected by either aloin and doxorubicin treatments. In conclusion, repeated aloin treatment, in contrast to that of doxorubicin, failed to produce oxidative stress‐induced cardiotoxicity in the rats.

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Section: Discussionsupporting

confidence: 63%

In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

Esmat

Said

Hamdy

et al. 2012

Drug Development Research

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“…DOX accumulates in the BCEC nucleus as shown by our fluorescence study (data not shown), and this accumulation leads to a BBB disruption. Indeed, DOX is capable of generating a variety of free radical species that are toxic for the cells (Keizer et al, 1990;Leblanc et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Effects of γ- and Hydroxypropyl-γ-cyclodextrins on the Transport of Doxorubicin across an in Vitro Model of Blood-Brain Barrier

Monnaert¹,

Betbeder²,

Fénart³

et al. 2004

J Pharmacol Exp Ther

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Association between doxorubicin (DOX) and ␥-cyclodextrin (␥-CD) or hydroxypropyl-␥-CD (HP-␥-CD) has been examined to increase the delivery of this antitumoral agent to the brain. The stoichiometry and the stability constant of ␥-CD or HP-␥-CD and DOX complexes were determined in physiological medium by UV-visible spectroscopy. By using an in vitro model of the blood-brain barrier (BBB), endothelial permeability and toxicity toward the brain capillary endothelial cells of DOX, ␥-CD, and HP-␥-CD were performed. For each CD, endothelial permeability was relatively low and a disruption of the BBB occurred at 20 M, 20 mM, and 50 mM DOX, ␥-CD, and HP-␥-CD, respectively. Increasing amounts of CDs were added to a fixed DOX concentration. Addition of ␥-CD or HP-␥-CD, up to 15 and 35 mM, respectively, decreased the DOX delivery, probably due to the low complex penetration across the BBB and the decrease in free DOX concentration. Higher CD concentrations increased the DOX delivery to the brain, but this effect is due to a loss of BBB integrity. In contrast to what was observed on Caco-2 cell model with various drugs, CDs are not able to increase the delivery of DOX across our in vitro model of BBB.

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“…Indeed, DOX is capable of generating a variety of free radical species which are toxic for the cells (Keizer et al, 1990;Leblanc et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

DMEM (Dulbecco’s Modified Eagle’s Medium)

2006

Cold Spring Harb Protoc

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Nucleolar Organizer Regions in Cardiac Lesions Induced by Doxorubicin

Cited by 13 publications

References 41 publications

In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

Effects of γ- and Hydroxypropyl-γ-cyclodextrins on the Transport of Doxorubicin across an in Vitro Model of Blood-Brain Barrier

DMEM (Dulbecco’s Modified Eagle’s Medium)

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