Evaluation of amino acids as mediators for the antibacterial activity of iodine-lithium-alpha-dextrin in vitro and in vivo.
OBJECTIVE
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.
Davtyan
Tigran K
TK
Laboratory of Immunology and Virology, Armenicum Research Center, Yerevan, Republic of Armenia. tigdav@excite.com
Hakobyan
Isabelle S
IS
Muradyan
Rafael E
RE
Hovhannisyan
Hrachya G
HG
Gabrielyan
Emil S
ES
D000596:Amino Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000382:microbiology / Q000517:prevention & control; D015169:Colony Count, Microbial; D003470:Culture Media; D003912:Dextrins / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D048168:Escherichia coli K12 / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006219:Halogens / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007455:Iodine / Q000494:pharmacology* / Q000627:therapeutic use; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control; D013268:Stimulation, Chemical
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D003470:Culture Media; D003912:Dextrins; D004338:Drug Combinations; D006219:Halogens; D018020:Lithium Compounds; D007455:Iodine