Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial-Dependent Apoptosis

Figure 7

Early perfusion of CsA in isolated hearts ameliorates the Cas effect due to MPT opening. RPP is shown in (a). The decline in contractility due to the perfusion (20 min) of 10 μM III-Ea alone is presented as the blue trace. The early perfusion (10 min) of 1 μM CsA (white squares) delays the decline in contractility due to the subsequent perfusion with III-Ea. The control trace is presented as the black trace. Analysis of the traces is presented as the time for half inhibition (t_0.5) (b). Experiments in isolated mitochondria prepared from these hearts at the end of perfusion. Representative recording of membrane potential (c) and Ca²⁺ retention capacity (d). Semiquantitative analysis of mitochondrial CRC (e). Mitochondria from III-Ea-treated hearts are represented as a blue solid line, mitochondria from CsA-Cas III-Ea hearts as a blue dot line, and untreated hearts as a black solid line. Arrows indicates succinate (10 mM), CCCP (0.08 μM), or 10 μM pulses of Ca²⁺ addition. Values are mean ± SEM. versus control; versus (C) III-Ea ( animals for each treatment).

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