Functioning of the hemostasis system under the action of chitosan in the conditions of impaired fat metabolism in rats

Abstract

Ongoing studies are aimed at improving the effectiveness of the hemostatic drug chitosan that simultaneously affects fat metabolism. However, the effect of chitosan on fibrin polymerization and the state of primary and plasma hemostasis in metabolic disorders has not been sufficiently studied. The aim of the study was to investigate the effect of repeated oral chitosan administration on functioning of the hemostasis system in rats with impaired fat metabolism. Methods. In experiments conducted in compliance with ethical rules, 50 male Wistar rats weighing 250-280 g with predeveloped metabolic disorders were injected orally with water-soluble chitosan (succinyl chitosan). The animals continued receiving a high-calorie diet throughout the entire experimental period. The first group (Experiment) was administered chitosan orally at a daily dose of 100 mg/kg for 14 days; the second group (Control) was similarly administered 0.85% NaCl. Untreated animals (Normal) were kept on a standard commercial rat food and did not receive any drugs. Blood was collected from the jugular vein 20 h after the last, 14^th administration of drugs and 7 days after the drug withdrawal. Standard coagulometric methods were used. Results. At 20 h after the 14th administration of chitosan to rats with impaired fat metabolism, an increase in blood clotting was found, which included decreases in the fibrinolytic potential and the plasmin activity, and an increase in the fibrin polymerization. These changes remained also at 7 days after the drug was discontinued while the high-calorie diet was continued. Conclusion. For the first time, this study showed that chitosan was able to decrease significantly the plasmin activity and the fibrinolytic potential, and to increase the fibrin polymerization associated with an increase in activated partial thromboplastin time (APTT) in rats with metabolic disorders. Possible mechanisms of the effect of the chitosan derivative on hemostatic and fibrinolytic processes are discussed.