Premium
Potential Hemorrhagic Effects of K5‐Derivatives of Bacterial Origin : Practical Implications to Develop New Class of Heparin‐like Drugs
Author(s) -
Maddineni Jyothi,
Cornelli Umberto,
Mai Marco,
Hoppensteadt Debra,
Fareed Jawed
Publication year - 2006
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.20.4.a266-d
Subject(s) - heparin , sulfation , saline , dose , in vivo , chemistry , pharmacology , polysaccharide , molecular mass , biochemistry , medicine , biology , enzyme , microbiology and biotechnology
The K5‐derived sulfaminoheparosans (SAHs) represent a group of sulfated polysaccharides, which structurally and functionally mimic heparins. These agents are obtained from bacterial core polysaccharide of E.coli, which are chemically (deacetylation, N‐sulfation and O‐sulfation) and enzymatically (C5‐epimerization) transformed to obtain the similar chemical characteristics as of heparin. This study was designed to determine the potential hemorrhagic effects of two SAH fractions (bio‐20 kDa and bio‐6 kDa) with mean molecular weights of 20 and 6 kDa in vivo using a tail transsection model. Method The agents were administered intravenously to male Sprague‐Dawley rats (n = 5), at two different dosages of 0.25 and 2.5 mg/kg. The bleeding potential was assessed 5 minutes post administration. Saline was used as control and Unfractionated heparin (UFH) was used as the reference compound. Results At 0.25 mg/kg, the bio‐6 kDa, bio‐20 kDa and UFH prolonged the bleeding times (676 ± 81, 750 ± 75 and 850 ± 65 respectively) significantly (p < 0.01) relative to the saline control (376 ± 127). At 2.5 mg/kg, both the bio‐6 kDa, bio‐20 kDa and UFH produced significantly (p < 0.01) higher hemorrhagic effects with prolonged bleeding times of 1030 ± 260, 700 ± 101 and 1220 ± 121 seconds respectively, compared to the control (376 ± 127 sec). However, only UFH and bio‐6 kDa were able to significantly (p < 0.05) increase the bleeding times compared to the bio‐20 kDa. Conclusions The reported results clearly suggest that the SAHs exhibit similar hemorrhagic effects as of UFH. Thus these agents represent a new class of heparin like drugs, which can be further validated for the indications of various thrombotic disorders.