The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine
Previous studies have indicated that the generation of H2O2 may be a key step in the mechanism mediating the in vitro cytotoxicity of 3-hydroxykynurenine (3HK). An exposure protocol resulting in a delayed toxicity was utilized in order to further examine the role of H2O2 in the in vitro toxicity of...
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| Veröffentlicht in: | Neurochemical research 1990-11, Vol.15 (11), p.1101-1107 |
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| container_title | Neurochemical research |
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| creator | EASTMAN, C. L GUILARTE, T. R |
| description | Previous studies have indicated that the generation of H2O2 may be a key step in the mechanism mediating the in vitro cytotoxicity of 3-hydroxykynurenine (3HK). An exposure protocol resulting in a delayed toxicity was utilized in order to further examine the role of H2O2 in the in vitro toxicity of 3HK in a neural hybrid cell line. 3HK-induced cell lysis was significantly attenuated by administration of catalase after termination of 3HK exposure and was abolished when intracellular peroxidase activity was elevated by pretreatment of cultures with horseradish peroxidase. In addition, a dose-dependent attenuation of 3HK toxicity was observed when cultures were exposed to 3HK in the presence of the iron chelator, desferrioxamine (DFO). Pretreatment with DFO also resulted in a significant attenuation of 3HK toxicity. These data suggest a direct role for H2O2 and metal ions in the cytotoxic action of 3HK and indicate that cell lysis results from the intracellular accumulation of toxic levels of H2O2. |
| doi_str_mv | 10.1007/BF01101711 |
| format | Article |
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L</creatorcontrib><creatorcontrib>GUILARTE, T. R</creatorcontrib><title>The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><description>Previous studies have indicated that the generation of H2O2 may be a key step in the mechanism mediating the in vitro cytotoxicity of 3-hydroxykynurenine (3HK). An exposure protocol resulting in a delayed toxicity was utilized in order to further examine the role of H2O2 in the in vitro toxicity of 3HK in a neural hybrid cell line. 3HK-induced cell lysis was significantly attenuated by administration of catalase after termination of 3HK exposure and was abolished when intracellular peroxidase activity was elevated by pretreatment of cultures with horseradish peroxidase. In addition, a dose-dependent attenuation of 3HK toxicity was observed when cultures were exposed to 3HK in the presence of the iron chelator, desferrioxamine (DFO). Pretreatment with DFO also resulted in a significant attenuation of 3HK toxicity. These data suggest a direct role for H2O2 and metal ions in the cytotoxic action of 3HK and indicate that cell lysis results from the intracellular accumulation of toxic levels of H2O2.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Catalase - metabolism</subject><subject>Cell metabolism, cell oxidation</subject><subject>Cell physiology</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Deferoxamine - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Histocytochemistry</subject><subject>Horseradish Peroxidase</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Iron Chelating Agents - pharmacology</subject><subject>Kynurenine - analogs & derivatives</subject><subject>Kynurenine - antagonists & inhibitors</subject><subject>Kynurenine - toxicity</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Tumor Cells, Cultured</subject><issn>0364-3190</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkD1PwzAURS0EKqWwsCNlgQEp8F4cO8kIFQWkSgipzFE-nqkhjYudoObfk7YRne5wzr3DZewS4Q4BovvHGSACRohHbIwi4r5MgB-zMXAZ-hwTOGVnzn0B9HqAIzYKIE4CmYzZ-2JJnjUVeUZ5y6605pNqb03WbHRJnq69ZrmLX91Y4xVdY5oeFbrptg3u7zqb7rurW0u1rumcnaiscnQx5IR9zJ4W0xd__vb8On2Y-0Ug4saPMc9KUknAIQohQYkKVa4gQhEKGaMSBZY5qTJELqXIRRwGOYkMIgpVUBKfsJv97tqan5Zck660K6iqsppM61IUicRYQi_e7sXCGucsqXRt9SqzXYqQbv9LD__18tWw2uYrKv_V4bCeXw88c0VWKZvVhXaHxUSEvcj5H7xLdzA</recordid><startdate>199011</startdate><enddate>199011</enddate><creator>EASTMAN, C. 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Psychology</topic><topic>Histocytochemistry</topic><topic>Horseradish Peroxidase</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Iron Chelating Agents - pharmacology</topic><topic>Kynurenine - analogs & derivatives</topic><topic>Kynurenine - antagonists & inhibitors</topic><topic>Kynurenine - toxicity</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EASTMAN, C. L</creatorcontrib><creatorcontrib>GUILARTE, T. 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An exposure protocol resulting in a delayed toxicity was utilized in order to further examine the role of H2O2 in the in vitro toxicity of 3HK in a neural hybrid cell line. 3HK-induced cell lysis was significantly attenuated by administration of catalase after termination of 3HK exposure and was abolished when intracellular peroxidase activity was elevated by pretreatment of cultures with horseradish peroxidase. In addition, a dose-dependent attenuation of 3HK toxicity was observed when cultures were exposed to 3HK in the presence of the iron chelator, desferrioxamine (DFO). Pretreatment with DFO also resulted in a significant attenuation of 3HK toxicity. These data suggest a direct role for H2O2 and metal ions in the cytotoxic action of 3HK and indicate that cell lysis results from the intracellular accumulation of toxic levels of H2O2.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>2089269</pmid><doi>10.1007/BF01101711</doi><tpages>7</tpages></addata></record> |
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| ispartof | Neurochemical research, 1990-11, Vol.15 (11), p.1101-1107 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Biological and medical sciences Catalase - metabolism Cell metabolism, cell oxidation Cell physiology Cell Survival - drug effects Cell Survival - physiology Deferoxamine - pharmacology Fundamental and applied biological sciences. Psychology Histocytochemistry Horseradish Peroxidase Hydrogen Peroxide - metabolism Iron Chelating Agents - pharmacology Kynurenine - analogs & derivatives Kynurenine - antagonists & inhibitors Kynurenine - toxicity L-Lactate Dehydrogenase - metabolism Molecular and cellular biology Tumor Cells, Cultured |
| title | The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine |
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