Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies

被引：50

作者：

Wolf, Armin ^{[1
]}

Couttet, Philippe ^{[1
]}

Dong, Min ^{[1
]}

Grenet, Olivier ^{[1
]}

Heron, Marcia ^{[2
]}

Junker, Ursula ^{[1
]}

Laengle, Ulrich ^{[1
]}

Ledieu, David ^{[1
]}

Marrer, Estelle ^{[1
]}

Nussher, Anja ^{[1
]}

Persohn, Elke ^{[1
]}

Pognan, Francois ^{[1
]}

Riviere, Gilles-Jacques ^{[3
]}

Roth, Daniel Robert ^{[1
]}

Trendelenburg, Christian ^{[1
]}

Tsao, Jeffrey ^{[4
]}

Roman, Danielle ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Preclin Safety, CH-4009 Basel, Switzerland

[2] Novartis Inst Biomed Res, Cardiovasc Physiol, Cambridge, MA USA

[3] Novartis Inst Biomed Res, Drug Metab & Pharmacokinet, Basel, Switzerland

[4] Novartis Inst Biomed Res, Global Imaging Grp, Cambridge, MA USA

来源：

LEUKEMIA RESEARCH | 2010年 / 34卷 / 09期

关键词：

Imatinib; Cardiotoxicity; c-Abl; Cardiomyocytes; Fibroblasts; siRNA knock down; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; PATIENTS RECEIVING IMATINIB; ABL TYROSINE KINASE; BCR-ABL; THERAPEUTIC AGENT; HEART-FAILURE; RAT-HEART; FOLLOW-UP; CELLS;

D O I：

10.1016/j.leukres.2010.01.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cytotoxic concentrations of imatinib mesylate (10-50 mu M) were required to trigger markers of apoptosis and endoplasmic reticulum stress response in neonatal rat ventricular myocytes and fibroblasts, with no significant differences observed between c-Abl silenced and nonsilenced cells. In mice, oral or intraperitoneal imatinib treatment did not induce cardiovascular pathology or heart failure. In rats, high doses of oral imatinib did result in some cardiac hypertrophy. Multi-organ toxicities may have increased the cardiac workload and contributed to the cardiac hypertrophy observed in rats only. These data suggest that imatinib is not cardiotoxic at clinically relevant concentrations (5 mu M). (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1180 / 1188

页数：9

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