Toxic Effects of Free and DNA-linked Daunorubicin on Isolated Rat Cardiac Myocytes
| Autor: | Allan Tomingas, Johan Högberg, Curt Peterson, Jovan Rajs, Irene Anundi, Christer Paul |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Lipid Peroxides Time Factors Daunorubicin In Vitro Techniques Biology Pharmacology Toxicology Lipid peroxidation DNA Adducts chemistry.chemical_compound Malondialdehyde hemic and lymphatic diseases polycyclic compounds medicine Animals Myocyte neoplasms Cardiotoxicity L-Lactate Dehydrogenase Heart Rats Inbred Strains DNA Rats carbohydrates (lipids) chemistry Toxicity Trypan blue Intracellular medicine.drug |
| Zdroj: | Acta Pharmacologica et Toxicologica. 51:292-299 |
| ISSN: | 0001-6683 |
| DOI: | 10.1111/j.1600-0773.1982.tb01029.x |
| Popis: | Isolated cardiac myocytes from adult rats were used as a model to study the cardiotoxicity of free and DNA-linked daunorubicin. The toxic effects on the myocytes were evaluated by studying morphological changes, trypan blue exclusion and cell membrane permeability to NADH, as determined by LDH-activity. At a concentration of 100 microM daunorubicin caused an increased plasma membrane permeability within 30 min. Using light microscopy, the myocytic injury induced by daunorubicin could be distinguished from that induced by anoxia or elevated pH. In contrast to the effect of the free drug, no toxic effects could be demonstrated after incubation with DNA-linked daunorubicin (100 microM) for 5 hours. The higher toxicity of the free drug was related to a much higher intracellular accumulation of daunorubicin. No fluorescent metabolites of daunorubicin could be detected in the myocardial cells. Daunorubicin did not induce lipid peroxidation, as judged by the absence of malondialdehyde production and evolution of ethane. It is concluded that daunorubicin exerts toxic effects on rat cardiac myocytes by mechanisms that do not involve lipid peroxidation. Isolated cardiac cells from adult rats seem to be a useful model for the further study of such mechanisms. |
| Databáze: | OpenAIRE |
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