Decreased Zinc Toxicity Resulting from Doxorubicin Without Increased GSSG Export in Three Human Lung Cell Lines
| Autor: | B. Fichtl, U. I. Walther, Harald Mückter, S. C. Walther |
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| Rok vydání: | 2004 |
| Předmět: |
inorganic chemicals
Thioredoxin-Disulfide Reductase Endocrinology Diabetes and Metabolism Clinical Biochemistry Glutathione reductase Pharmacology medicine.disease_cause Biochemistry Cell Line Inorganic Chemistry Excretion chemistry.chemical_compound Methionine Cell Line Tumor medicine Humans NADH NADPH Oxidoreductases Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 Lung A549 cell Glutathione Disulfide Chemistry Biochemistry (medical) General Medicine Glutathione Drug Resistance Multiple Zinc Glutathione Reductase Toxicity Zinc toxicity Glutathione disulfide Multidrug Resistance-Associated Proteins medicine.drug |
| Zdroj: | Biological Trace Element Research. 102:091-104 |
| ISSN: | 0163-4984 |
| DOI: | 10.1385/bter:102:1-3:091 |
| Popis: | Zinc-mediated cytotoxicity is recognized, at least in part, by a decrease of reduced glutathione (GSH) and an increase in the oxidized form of glutathione (GSSG). Doxorubicin is a common inducer of multidrug-resistance-associated proteins and such proteins might, furthermore, be associated by an increased GSSG export rate. Therefore, zinc-mediated toxicity should be abolished after doxorubicin pretreatment. In the present study, zinc toxicity was characterized by methionine incorporation, glutathione content, and the GSSG/GSH ratio. Experiments were performed in three established lung cell lines comparing doxorubicin-pretreated cells with controls. Zinc-mediated toxicity was significantly decreased after pretreatment with doxorubicin as assessed by methionine-incorporation inhibition, GSH depletion, and/or GSSG increase in the two nonmalignant cell lines. Unexpectedly, zinc-associated GSSG export was not increased after doxorubicin pretreatment. This inconsistency might be explained as a result of a decreased zinc content in these cells, probably because of an increased export rate of zinc. The findings are in contradiction to the opinion of metal excretion by multidrug-resistance-associated proteins, matched to GSH conjugate excretion, as it is discussed for cadmium, for example. |
| Databáze: | OpenAIRE |
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