In vitro Studies on the Cardiotoxicity of Chemotherapeutics

Publisher Website
Google Scholar
Abstract
The de novo synthesis of ‘shock proteins’ is a cellular reaction towards toxic agents. Therefore, the induction of ‘shock proteins’ serves as a detector of toxicity on the level of protein synthesis. We investigated the effects of chemotherapeutics on cultured cardiac myocytes with this test system. Cisplatin (≥16 μmol/l) and methotrexate (≥ 1.4 μmol/l) evoked the de novo formation of a 30-kilodalton ‘Shock protein’. Doxorubicin (80–0.8 μmol/l) and daunomycin (90–0.9 μmol/l) inhibited protein synthesis almost completely. The other chemotherapeutic drugs tested did not influence heart cell protein formation even at concentrations widely above the pharmacological range. Our results indicate that the anthracyclines probably exert cardiotoxicity by depression of protein synthesis. Cisplatin and methotrexate are potentially cardiotoxic at high concentrations.

This publication has 0 references indexed in Scilit: