Document Detail


Time-course of hypericin phototoxicity and effect on mitochondrial energies in EMT6 mouse mammary carcinoma cells.
MedLine Citation:
PMID:  9667489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Photoactivated hypericin produces singlet oxygen and superoxide anion radical; however, the intracellular events contributing to toxicity are unknown. Clonogenic assays of oxygen-dependent hypericin phototoxicity to EMT6 cells have previously shown that 0.5 microM hypericin + 1.5 J cm(-2) fluorescent light is non-toxic and that 1.0 microM hypericin + 1.5 J cm(-2) fluorescent light produces LD40 toxicity. Intracellular events leading to toxicity were revealed at these doses. Lactate dehydrogenase leakage was elevated for both 0.5 microM and 1.0 microM hypericin + light immediately following irradiation. While values eventually returned to control levels for 0.5 microM hypericin + light, leakage increased over time for 1.0 microM hypericin indicating reversible and irreversible toxicity, respectively. Increases in lipid and protein oxidation were measured immediately following irradiation; however, these parameters return to control levels within 0.5 h for both doses. Both total cellular ATP levels and cellular respiration were depressed by approximately 50% of control values for 1.0 microM hypericin + light. These values were unchanged for 0.5 microM hypericin + light. Along with previously reported data demonstrating that light-activated hypericin can inhibit mitochondial succinoxidase in beef heart mitochondria in vitro, these data support oxidative stress-initiated mitochondrial damage as a key target in hypericin phototoxicity.
Authors:
S A Johnson; A E Dalton; R S Pardini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  25     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1999-04-30     Completed Date:  1999-04-30     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  144-52     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Nevada, Reno 89557, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / analysis
Animals
Cell Membrane / drug effects,  radiation effects
Cell Respiration / drug effects,  radiation effects
Cell Survival / drug effects,  radiation effects
Dose-Response Relationship, Drug
Energy Metabolism / drug effects*,  radiation effects*
Female
Intracellular Fluid / chemistry
L-Lactate Dehydrogenase / analysis
Light
Lipid Peroxidation / drug effects,  radiation effects
Mammary Neoplasms, Animal
Mice
Mitochondria / drug effects*,  metabolism,  radiation effects
Oxidative Stress / drug effects,  radiation effects
Perylene / analogs & derivatives*,  toxicity
Photosensitizing Agents / toxicity
Protein Kinase C / antagonists & inhibitors
Proteins / drug effects,  metabolism,  radiation effects
Thiobarbituric Acid Reactive Substances / analysis
Time Factors
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Photosensitizing Agents; 0/Proteins; 0/Thiobarbituric Acid Reactive Substances; 198-55-0/Perylene; 548-04-9/hypericin; 56-65-5/Adenosine Triphosphate; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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