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Melatonin inhibits the protein c anticoagulant Pathway in rats

Emiliya Stancheva, Antoaneta Zarkova, Irina Pashalieva, Yuri Nyagolov, Negrin Negrev


This study examines the influence of melatonin on the PC anticoagulant pathway in rats. The experiment was performed on 52 male white Wistar rats weighing 200-220 g. Animals were equally divided into 4 groups. They were treated in three consecutive days, every 12 hours, subcutaneously: 1st group - with saline solution (solvent for melatonin and luzindole); 2nd group - with melatonin, daily dose 0.2 mg/kg body weight; 3rd group - with luzindole, nonstop dose of 0.4 mg/kg body weight; 4th group - melatonin, one hour after pretreatment with luzindole. The required amount of blood was taken under urethane narcosis via direct cardiac puncture. After three days of administration of melatonin, a significant decrease in the antigen concentration of protein C, protein C activity, activated protein C and thrombomodulin was observed. The soluble form of the endothelial receptor for protein C, activity of protein S and free protein S were significantly elevated. The competitive melatonin receptor antagonist - luzindole, when administered alone and in pretreatment, effectively removes the observed effects of melatonin by blocking exogenous, as well as endogenous melatonin. In conclusion, our data give us reason to assume that melatonin significantly reduces the activity of the protein C anticoagulant pathway in rats.


melatonin, protein C, protein S, thrombomodulin, sEPCR

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About The Authors

Emiliya Stancheva
Department of Physiology and Pathophysiology, Medical University - Varna

Antoaneta Zarkova
Specialized hospital for active treatment of hematological diseases of Sofia

Irina Pashalieva
Department of physiology and pathophysiology, Medical university of Varna

Yuri Nyagolov
Department of physiology, Medical university of Sofia

Negrin Negrev
Department of physiology and pathophysiology, Medical university of Varna

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