Document Detail


Phototoxicity of lumidoxycycline.
MedLine Citation:
PMID:  8370969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Doxycycline (DOTC) is a photosensitizing drug whose mechanism of phototoxicity is complicated by the large variety of stable photoproducts formed. To assess the role of a DOTC photoproduct, lumidoxycycline (LuDOTC), in the photosensitization mechanism of DOTC, MGH-U1 human bladder carcinoma cells were treated in vitro with either DOTC or LuDOTC, and irradiated with the 351-nm emission of an argon-ion laser. Both DOTC and LuDOTC were phototoxic and caused radiant-exposure-dependent inhibition of cellular incorporation of tritiated thymidine. On an absorbed-photon basis, DOTC was about five times as phototoxic as LuDOTC. Cellular uptake of DOTC was about five times as great as that of LuDOTC. Epifluorescence microscopy showed localization of LuDOTC predominantly within cellular membranes, particularly of mitochondria, as well as a low level of LuDOTC fluorescence diffusely within the cytoplasm. Epifluorescence microscopy of cells labeled with the mitochondrial probe, rhodamine 123, showed mitochondrial fragmentation and altered mitochondrial membrane integrity after LuDOTC photosensitization; these effects depended on radiant exposure and were partially reversible by 24 h after irradiation. For both DOTC and LuDOTC, phototoxicity was increased by irradiation in the presence of deuterium oxide and decreased in the presence of sodium azide, effects consistent with an important mechanistic role for singlet oxygen, O2(1 delta g), in the injury. In solution, LuDOTC and DOTC had similar quantum yields for generation of O2(1 delta g) as measured by time-resolved spectroscopy and by O2(1 delta g) trapping. LuDOTC was photostable in solution, but DOTC underwent significant photodegradation. These data demonstrate that DOTC photo-products such as LuDOTC have significant photobiologic activity and may play an important role in the phototoxicity mechanism of DOTC.
Authors:
C R Shea; G A Olack; H Morrison; N Chen; T Hasan
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  101     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-10-12     Completed Date:  1993-10-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  329-33     Citation Subset:  IM    
Affiliation:
Division of Dermatopathology, New York Hospital, Cornell University Medical College, New York.
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MeSH Terms
Descriptor/Qualifier:
Doxycycline / analogs & derivatives*,  chemistry,  toxicity
Humans
Intracellular Fluid / chemistry
Lasers
Nitrogen / pharmacology
Photochemistry*
Photosensitivity Disorders / chemically induced*
Photosensitizing Agents / metabolism
Tumor Cells, Cultured / radiation effects
Water / pharmacology
Grant Support
ID/Acronym/Agency:
5R01-AR39286/AR/NIAMS NIH HHS; R29-AR38918/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Photosensitizing Agents; 12136-83-3/sodium nitride; 134970-95-9/lumidoxycycline; 564-25-0/Doxycycline; 7727-37-9/Nitrogen; 7732-18-5/Water

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


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