title: Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies.
abstract: Cytotoxic concentrations of imatinib mesylate (10-50 microM) 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 microM).
authors.affiliation: Preclinical Safety, Novartis Institutes for Biomedical Research, CH-4009 Basel, Switzerland.
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.forename: Philippe
authors.initials: P
authors.lastname: Couttet
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Olivier
authors.initials: O
authors.lastname: Grenet
authors.forename: Marcia
authors.initials: M
authors.lastname: Heron
authors.forename: Ursula
authors.initials: U
authors.lastname: Junker
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laengle
authors.forename: David
authors.initials: D
authors.lastname: Ledieu
authors.forename: Estelle
authors.initials: E
authors.lastname: Marrer
authors.forename: Anja
authors.initials: A
authors.lastname: Nussher
authors.forename: Elke
authors.initials: E
authors.lastname: Persohn
authors.forename: Francois
authors.initials: F
authors.lastname: Pognan
authors.forename: Gilles-Jacques
authors.initials: GJ
authors.lastname: Rivière
authors.forename: Daniel Robert
authors.initials: DR
authors.lastname: Roth
authors.forename: Christian
authors.initials: C
authors.lastname: Trendelenburg
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tsao
authors.forename: Danielle
authors.initials: D
authors.lastname: Roman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001483:Base Sequence; D001549:Benzamides; D017931:DNA Primers; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D000068877:Imatinib Mesylate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate