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Yukio Kuramochi, Hisato Takagi, Toshisada Morita, Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumor suppression, European Heart Journal, Volume 27, Issue 21, November 2006, Pages 2610–2611, https://doi.org/10.1093/eurheartj/ehl293
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The article by Neilan et al.1 [May 27(10) issue of this journal] is of interest to us. Their group has documented that iloprost attenuates the doxorubicin (DOX)-induced cardiac cell death in vitro and in vivo.2,3 They extend the work and estimate the effect of iloprost on DOX-induced cardiac dysfunction and anti-cancer therapy. Their message is clear, but this study raises some questions.
The authors mention that cardiac sections from animals treated with iloprost+DOX show none of the pathological changes seen in the DOX group and are indistinguishable from controls. Certainly, iloprost attenuates DOX-triggered cardiac cell death and dysfunction. However, there are around 4–5% of cardiomyocyte loss even in iloprost+DOX group with a small increase of TUNEL-positive cells (cf. about 10% of cell reduction in DOX group; Figure 31). Why did the authors fail to detect such a huge change in histological analysis? Moreover, the degradation of titin, a critical sarcomere player in the regulation of contractile function, is an early event in DOX-induced cardiac injury and consequent necrosis.4 In this animal model, comparatively high dose of DOX was used in short duration, and it might induce cardiomyocyte necrosis rather than apoptosis.5 Therefore, myofibrillar disarray may be a better parameter than cardiac fibrosis to estimate acute DOX toxicity.
