Document Detail


Evaluation of amino acids as mediators for the antibacterial activity of iodine-lithium-alpha-dextrin in vitro and in vivo.
MedLine Citation:
PMID:  17439975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The systemic therapeutic application of iodophores has not yet been accepted due to limited availability of safe and effective ionized iodine preparations. Here we evaluated the antibacterial activity of iodine-lithium-alpha-dextrin (ILalphaD) both in vitro and in vivo. METHODS: The MIC values of ILalphaD against 189 bacterial isolates in various growth media and in vivo toxicity and protective efficacy of ILalphaD in preventing mortality of rats infected with Staphylococcus aureus were determined. The intracellular killing of S. aureus by neutrophils in the presence of ILalphaD and myeloperoxidase (MPO)-catalysed oxidation of iodide was also determined. RESULTS: The MIC values of ILalphaD against 189 Gram-positive cocci and Gram-negative bacilli ranged between 124-512 mg/L in growth media and 6.2-12.5 mg/L in buffer solution, and were highly variable in the presence of amino acids. We observed protection of S. aureus-infected rats from death with significant reduction of bacterial growth in organs upon intravenous administration of ILalphaD at doses that are 4-12 times lower than maximal in vivo tolerability dose. Intracellular killing of S. aureus by neutrophils increased in the presence of ILalphaD probably due to MPO-catalysed oxidation of iodide into hypoiodous acid. The pattern of ILalphaD reaction with amino acids at different pH or halide ion content determined both the generation of long-lived secondary oxidants and antibacterial activity. CONCLUSIONS: Systemic application of ILalphaD proved to be successful in the rat infection model by promoting host defence. Probable mechanisms are increased intracellular killing of bacteria by production of hypoiodous acid and iodamines as well as anti-inflammatory activity.
Authors:
Tigran K Davtyan; Isabelle S Hakobyan; Rafael E Muradyan; Hrachya G Hovhannisyan; Emil S Gabrielyan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-17
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  59     ISSN:  0305-7453     ISO Abbreviation:  J. Antimicrob. Chemother.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-17     Completed Date:  2007-08-17     Revised Date:  2007-09-10    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  England    
Other Details:
Languages:  eng     Pagination:  1114-22     Citation Subset:  IM    
Affiliation:
Laboratory of Immunology and Virology, Armenicum Research Center, Yerevan, Republic of Armenia. tigdav@excite.com
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / pharmacology*,  therapeutic use
Animals
Anti-Bacterial Agents / pharmacology*,  therapeutic use
Bacteria / drug effects*
Bacterial Infections / microbiology,  prevention & control
Colony Count, Microbial
Culture Media
Dextrins / pharmacology*,  therapeutic use
Dose-Response Relationship, Drug
Drug Combinations
Escherichia coli K12 / drug effects
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Halogens / pharmacology
Hydrogen-Ion Concentration
Iodine / pharmacology*,  therapeutic use
Lithium Compounds / pharmacology*,  therapeutic use
Male
Neutrophils / drug effects,  microbiology
Oxidation-Reduction
Phagocytosis / drug effects
Rats
Rats, Wistar
Staphylococcal Infections / microbiology,  prevention & control
Stimulation, Chemical
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Anti-Bacterial Agents; 0/Culture Media; 0/Dextrins; 0/Drug Combinations; 0/Halogens; 0/Lithium Compounds; 7553-56-2/Iodine

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


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