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JAC Advance Access published online on April 17, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm094
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Evaluation of amino acids as mediators for the antibacterial activity of iodine-lithium-{alpha}-dextrin in vitro and in vivo

Tigran K. Davtyan1,*, Isabelle S. Hakobyan1, Rafael E. Muradyan2, Hrachya G. Hovhannisyan3 and Emil S. Gabrielyan2

1 Laboratory of Immunology and Virology, Armenicum Research Center, Yerevan, Republic of Armenia 2 Drug and Medical Technology Agency of Ministry of Health, Yerevan, Republic of Armenia 3 Institute of Microbiology of Armenian National Academy of Sciences, Abovyan, Republic of Armenia

* Corresponding author. Tel: +374-1-74-14-31; Fax: +374-1-54-80-13; E-mail: tigdav{at}excite.com

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 (IL{alpha}D) both in vitro and in vivo.

Methods: The MIC values of IL{alpha}D against 189 bacterial isolates in various growth media and in vivo toxicity and protective efficacy of IL{alpha}D in preventing mortality of rats infected with Staphylococcus aureus were determined. The intracellular killing of S. aureus by neutrophils in the presence of IL{alpha}D and myeloperoxidase (MPO)-catalysed oxidation of iodide was also determined.

Results: The MIC values of IL{alpha}D 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 IL{alpha}D 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 IL{alpha}D probably due to MPO-catalysed oxidation of iodide into hypoiodous acid. The pattern of IL{alpha}D 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 IL{alpha}D 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.

Key Words: intracellular killing , iodophores , myeloperoxidase-catalysed oxidation of iodide , microbiocides


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