Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants
| Autor: | Dagmar Syrova, Andrea Sovcikova, Miroslav Ferenčík, Zuzana Seemannova, Zuzana Drobná, Katarína Horáková, Katarı́na Bušányová |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Antioxidant
Cell Survival medicine.medical_treatment Tetrazolium Salts Enzyme-Linked Immunosorbent Assay Pharmacology Biochemistry Antioxidants Xenobiotics Superoxide dismutase chemistry.chemical_compound Superoxides Physiology (medical) Cyclosporin a Toxicity Tests Benzo(a)pyrene medicine Humans Cycloheximide Cytotoxicity Cell damage Fluorenes Formazans Dose-Response Relationship Drug biology Superoxide Dismutase Chemistry Cell growth Superoxide medicine.disease Citrinin Mitochondria Toxicity Cyclosporine biology.protein Colorimetry Quercetin Lysosomes Oxidoreductases Cell Division HeLa Cells |
| Zdroj: | Free Radical Biology and Medicine. 30:650-664 |
| ISSN: | 0891-5849 |
| Popis: | The mode of the cytotoxic activity of three benzo(c)fluorene derivatives was characterized. The observed morphological changes of lysosomes or variations of mitochondrial activity are assumed to be the consequence of cell protection against oxidative damage and/or the part of the damage process. To establish the relationship between the quantity of superoxide (O2•−) generated and the degree of damage resulting from O2•−, a simple system based on measurement of 3-(4-iodophenyl)-2-(4-nitrophenyl)-5-phenyltetrazolium chloride (INT) reductase activity in the presence of superoxide dismutase (SOD) was used. The functionality of the chosen battery of in vitro tests was proved using several known superoxide inducers: cyclosporin A (CsA) and benzo(a)pyrene (BP), as well as noninducers: citrinin (CT) and cycloheximide (CH). From the results followed that the cell growth tests are much better indices of toxicity than the other tests. The model system for the evaluation of the protective capacity of antioxidants against superoxide-induced cytotoxicity included simultaneous exposure of HeLa cells to cytotoxic drugs and to quercetin (Qe), an antioxidant of plant origin. The complete abolishment of the inhibition of cell proliferation and clonogenic survival was concluded to be due to the protective effect of the antioxidant. These observations correlated with the decrease of superoxide content as estimated by the INT-reductase assay in the presence of SOD using the same model system, as well as with the increase of intracellular SOD content and its activity. |
| Databáze: | OpenAIRE |
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