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Effects of Medium Molecular Weight Heparinyl Phenylalnine on Superoxide Dismutase Activity in Mice
Seiichi Takeda1, Takao Toda2, Kazuki Nakamura3
1Research and Development Center, Fuso Pharmaceutical Industries LTD., Osaka, Japan sei-takeda@fuso-pharm.co.jp.
Abstract:
We investigated the radical scavenging ability of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF) and medium molecular weight heparinyl leucine (MHL) in the blood of mice. The extracellular superoxide dismutase (EC-SOD) activity was measured according to the method by Oyanagui and Sato. As a result, HE significantly increased the EC-SOD activity with a significant prolongation of activated partial thromboplastin time (APTT), while MHF and MHL significantly increased the EC-SOD activity without a prolongation of APTT. Dose-response curve at 20 min after the injection of each compound indicated a bell-shape. Changes in the plasma EC-SOD activity of mice after the administration of HE, MHF and MHL (10 mg/kg/10 ml) were investigated time-dependently. The plasma EC-SOD activity peaked at 5 min after the administration of all compounds. These results indicated that MHF and MHL show a radical scavenging ability by increasing the EC-SOD activity and MHF may be a candidate for clinical use.
Insights
Medium molecular weight heparinyl phenylalanine (MHF) and leucine (MHL) enhance radical scavenging by increasing extracellular superoxide dismutase (EC-SOD) activity without affecting blood clotting time. MHF shows potential for clinical use.
Area of Science:
- Biochemistry
- Pharmacology
- Biomedical Science
Background:
- Heparin (HE) derivatives are investigated for their biological activities.
- Extracellular superoxide dismutase (EC-SOD) plays a crucial role in antioxidant defense.
- Understanding the radical scavenging properties of modified heparins is important for therapeutic development.
Purpose of the Study:
- To evaluate the radical scavenging ability of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) in mice.
- To assess the impact of these compounds on extracellular superoxide dismutase (EC-SOD) activity and activated partial thromboplastin time (APTT).
Main Methods:
- In vivo administration of HE, MHF, and MHL to mice.
- Measurement of plasma EC-SOD activity using the Oyanagui and Sato method.
- Monitoring of activated partial thromboplastin time (APTT) to assess anticoagulant effects.
- Time-dependent and dose-response analyses of EC-SOD activity.
Main Results:
- Both HE, MHF, and MHL significantly increased plasma EC-SOD activity.
- HE administration led to a significant prolongation of APTT, indicating anticoagulant effects.
- MHF and MHL increased EC-SOD activity without significantly altering APTT.
- Plasma EC-SOD activity peaked at 5 minutes post-administration for all compounds, with a bell-shaped dose-response curve.
Conclusions:
- MHF and MHL demonstrate radical scavenging ability through the enhancement of EC-SOD activity.
- Unlike HE, MHF and MHL do not prolong APTT, suggesting a safer anticoagulant profile.
- MHF is identified as a potential candidate for clinical applications due to its efficacy and safety profile.
