Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice.

We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo.