Full text
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| Author(s): |
Julia Modesto Vicente
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2022-11-09 |
| Examining board members: |
Gabriel Forato Anhê;
Nicola Amanda Conran Zorzetto;
Fernando Abdulkader
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| Advisor: | Gabriel Forato Anhê |
| Abstract | |
Several studies have pointed to depression as an independent risk factor for the onset of cardiovascular diseases. One of the reasons for this correlation is the exacerbation of platelet activity observed in patients diagnosed with Major Depressive Disorder (MDD). Among the therapeutic possibilities, agomelatine (Valdoxan ®), a drug with melatoninergic properties, is an option in the treatment of DDM. Its differential consists of the agonist property on MT1 and MT2 receptors and, in parallel, blockade of serotoninergic 5-HT2C receptors. Although there are reports that platelet aggregation is inhibited by melatonin and potentiated by serotonin, it has not been established whether agomelatine is capable of interfering with platelet functional parameters. Thus, this study aims to analyze whether agomelatine could inhibit platelet activity and whether these possible effects are due to the activation of MT1/MT2 receptors. Venous blood samples from healthy volunteers, aged 18 to 60 years, of both sexes, were processed to obtain platelet-rich plasma (PRP) and washed platelets (PL) for cell viability assays, platelet aggregation induced by several agonists, quantification of thromboxane production, intracellular calcium mobilization, quantification of intracellular cyclic nucleotides, static platelet adhesion, GPIIb/IIIa (?IIb?3) integrin conformation change and p-selectin expression. Blood samples from C57BL6J isogenic mice were used for platelet aggregation and adhesion assays for comparative purposes. The results obtained indicated that agomelatine reduces fibrinogen adhesion, as well as platelet aggregation, thromboxane production, calcium mobilization and p-selectin expression, all of which are induced by arachidonic acid, while increasing intracellular levels of cAMP. This action is possibly dependent on melatoninergic receptors, as the use of MT1/MT2 antagonists prevented this effect. It is concluded that the use of agomelatine shows promise in the prevention of cardiovascular events resulting from platelet dysfunction (AU) | |
| FAPESP's process: | 19/19488-0 - The effect of agomelatine in human platelets aggregation and adhesion |
| Grantee: | Julia Modesto Vicente |
| Support Opportunities: | Scholarships in Brazil - Master |