Effect of PSC 833, verapamil and amiodarone on adriamycin toxicity in cultured rat cardiomyocytes

Estévez, M. D.; Wolf, Armin; Schramm, Ursula

doi:10.1016/s0887-2333(99)00087-9

Cited by 38 publications

(38 citation statements)

References 17 publications

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“…In Wistar rats, mdr1a gene expression was observed using RT-PCR; the signal seemed stronger in cultured myocytes than in cardiac tissue from adult and newborn rats suggesting an mdr1a cardiac expression more specifically localized into myocytes (Cayre et al, 1996). This was confirmed a few years later by the study of Estevez et al (2000), who demonstrated for the first time by immunohistochemistry (JSB-1 antibody) the expression of the P-gp protein in cardiomyocytes. The P-gp transporter was also found to be present in endothelial luminal membranes in rat heart although not restricted to this site (Beaulieu et al, 1997).…”

Section: Abc Transporters and Distribution Of Drugs To The Heartmentioning

confidence: 84%

See 1 more Smart Citation

The ATP-Binding Cassette Transporters and Their Implication in Drug Disposition: A Special Look at the Heart

Couture

Nash²,

Turgeon³

2006

Pharmacol Rev

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Section: Abc Transporters and Distribution Of Drugs To The Heartmentioning

confidence: 84%

“…In vitro Neonatal Wistar rat Estevez et al (2000) Myocardial uptake of idarubicin (anticancer) was increased by verapamil…”

Section: B Cardiotoxicity Related To Atp-binding Cassette Transportersmentioning

confidence: 99%

The ATP-Binding Cassette Transporters and Their Implication in Drug Disposition: A Special Look at the Heart

Couture

Nash²,

Turgeon³

2006

Pharmacol Rev

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“…The fact that only V max,12 but not K m,12 is affected suggests a noncompetitive interaction in accordance with the interaction between anthracyclines and verapamil in MDR cells (Nielsen et al, 1995;Stein, 1997). It has been shown that Pgp is expressed in heart tissue (van der Valk et al, 1990;Cayre et al, 1996;Beaulieu et al, 1997;Estevez et al, 2000), and that Pgp has a role in the cardiac uptake of anthracyclines was recently suggested by pharmacokinetic studies in mice lacking mdr1a Pgp [mdr1a (Ϫ/Ϫ) mice] (van Asperen et al, 1999b). The quantitative analysis of uptake kinetics after a 10-min infusion of idarubicin described herein extends considerably our previous observation that verapamil decreased the recovery of idarubicin in a washout experiment after 1-min infusion (Kang and Weiss, 2001).…”

Section: Myocardial Uptake and Effects Of Idarubicin 691mentioning

confidence: 92%

“…In contrast to the brain, where the Pgp pump is located on the luminal side of the capillary endothelial cell (Beaulieu et al, 1997), its location is less clear in the heart. Although Pgp is present in the plasma membrane of cardiomyocytes (Cayre et al, 1996;Estevez et al, 2000) and our kineticdynamic model indicates that compartment 2 represents the cytosol (see below), we cannot differentiate between capillary wall and sarcolemma as permeability barriers.…”

Section: Myocardial Uptake and Effects Of Idarubicin 691mentioning

confidence: 98%

P-Glycoprotein Inhibitors Enhance Saturable Uptake of Idarubicin in Rat Heart: Pharmacokinetic/Pharmacodynamic Modeling

Weiß

Kang²

2002

J Pharmacol Exp Ther

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Little is known about cardiac uptake kinetics of idarubicin, including a possible protective role of P-glycoprotein (Pgp)-mediated transport. This study therefore investigated uptake and negative inotropic action of idarubicin in the single-pass isolated perfused rat heart by using a pharmacokinetic/pharmacodynamic modeling approach. Idarubicin was administered as a 10-min constant infusion of 0.5 mg followed by a 70-min washout period in the absence and presence of the Pgp antagonists verapamil or amiodarone. Outflow concentration and left ventricular developed pressure were measured and the model parameters were estimated by simultaneous nonlinear regression. The results indicate the existence of a saturable, Michaelis-Menten type uptake process into the heart (K m ϭ 3.06 M, V max ϭ 46.0 M/min). Verapamil and amiodarone significantly enhanced the influx rate (V max increased 1.8-fold), suggesting that idarubicin is transported by Pgp directly out of the membrane before it gets into the cell. Verapamil and amiodarone attenuated the negative inotropic action of idarubicin, which was linked to the intracellular concentration of idarubicin.

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“…Isolation and cultivation of rat cardiomyocytes Primary cultures of cardiomyocytes from neonatal (2-4 days old) Wistar rats were prepared according to the published method [20] . The cell suspension was adjusted to a density of 3×10 5 -5×10 5 cells/mL and seeded in 6-or 96-well plastic plates.…”

Section: Histopathological Examinationsmentioning

confidence: 99%

Protective effect of tetrahydroxystilbene glucoside on cardiotoxicity induced by doxorubicin in vitro and in vivo

Zhang

Wang

2009

Acta Pharmacol Sin

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Aim:To test the effect of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) on doxorubicin (DOX)-induced cardiotoxicity. Methods: We used neonate rat cardiomyocytes and an acute mouse model of DOX-induced cardiotoxicity to examine the protective effect of THSG. Results: In the mouse model, administration of THSG signifi cantly reduced DOX-induced cardiotoxicity, including animal mortality, histopathological changes, and levels of serum creatine kinase (CK) and lactate dehydrogenase (LDH). Moreover, THSG was able to attenuate the increased malondialdehyde (MDA) and decreased reduced glutathione (GSH) caused by DOX. In in vitro studies, THSG 10−300 μmol/L ameliorated DOX-induced cardiomyocyte apoptosis in a concentration-dependent manner. Further studies showed that THSG inhibited reactive oxygen species (ROS) generation and prevented DOX-induced loss of mitochondrial membrane potential, caspase-3 activation and upregulation of Bax protein expression. We observed a protective response against damage after DOX treatment. The level of Bcl-2 protein was increased. Additionally, THSG inhibited a DOX-induced [Ca 2+ ] increase. Conclusion: These results showed that THSG protected against DOX-induced cardiotoxicity by decreasing ROS generation and intracellular [Ca 2+ ] and by inhibiting apoptotic signaling pathways.

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Effect of PSC 833, verapamil and amiodarone on adriamycin toxicity in cultured rat cardiomyocytes

Cited by 38 publications

References 17 publications

The ATP-Binding Cassette Transporters and Their Implication in Drug Disposition: A Special Look at the Heart

The ATP-Binding Cassette Transporters and Their Implication in Drug Disposition: A Special Look at the Heart

P-Glycoprotein Inhibitors Enhance Saturable Uptake of Idarubicin in Rat Heart: Pharmacokinetic/Pharmacodynamic Modeling

Protective effect of tetrahydroxystilbene glucoside on cardiotoxicity induced by doxorubicin in vitro and in vivo

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