Premium
Improvement of HDL and atherosclerosis by a mimetic peptide (18A) complexed with niclosamide and administered orally to mice (LB532)
Author(s) -
Madahian Sepideh,
Pourtabatabaei Nasim,
Navab Kaveh Daniel,
Safar Sheila,
Vazirian Samra,
Seyedali Seyedehsara,
Hough Greg
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb532
Subject(s) - niclosamide , oral administration , apolipoprotein e , medicine , chemistry , cholesterol , endocrinology , pharmacology , biology , disease , ecology
18A was incubated together with niclosamide and within 6h of oral administration there was significant improvement (p<0.001) in the HDL‐inflammatory index (HII) in ApoE null mice. Oral L‐4F alone or niclosamide alone were ineffective. Subcutaneous injection of L‐4F alone but not niclosamide alone significantly improved the HII. Analysis of the L‐4F‐niclosamide complex by gradient gel electrophoresis or Fourier Transform Infrared Spectroscopy indicated that the self‐association of L‐4F was altered resulting in smaller micelles. Oral administration of L‐4F and niclosamide to old apoE null mice together with pravastatin resulted in regression of lesions. In another experiment ApoE null mice 3‐4 months of age were treated for 7 months with pravastatin in the drinking water and oral L‐4F together with niclosamide in doses which produced maximal L‐4F plasma concentrations of ~100 ng/mL. There was a significant reduction in lesion area compared to controls (p<0.001). The reduction in lesion area was not improved by administering L‐4F subcutaneously for the first 3 months to achieve maximal L‐4F plasma concentrations ranging from 5 ‐ >45 μg/mL. These results suggest that regimens achieving initial high L‐4F plasma concentrations followed by oral administration may be no more effective than oral treatment alone which produces maximal L‐4F plasma concentration.