RESUMO
BACKGROUND: Flavonoids have been characterized as a prominent class of compounds to treat thrombotic diseases through the inhibition of thiol isomerases. Syzygium cumini is a flavonoid-rich medicinal plant that contains myricetin and gallic acid. Little is known about the potential antiplatelet properties of S. cumini and its constituent flavonoids. OBJECTIVE: To evaluate the antiplatelet effects and mechanism of action of a polyphenol-rich extract (PESc) from S. cumini leaf and its most prevalent polyphenols, myricetin and gallic acid. METHODS: PESc, myricetin, and gallic acid were incubated with platelet-rich plasma and washed platelets to assess platelet aggregation and activation. In vitro platelet adhesion and thrombus formation as well as in vivo bleeding time were performed. Finally, myricetin was incubated with recombinant thiol isomerases to assess its potential to bind and inhibit these, while molecular docking studies predicted possible binding sites. RESULTS: PESc decreased platelet activation and aggregation induced by different agonists. Myricetin exerted potent antiplatelet effects, whereas gallic acid did not. Myricetin reduced the ability of platelets to spread on collagen, form thrombi in vitro without affecting hemostasis in vivo. Fluorescence quenching studies suggested myricetin binds to different thiol isomerases with similar affinity, despite inhibiting only protein disulfide isomerase (PDI) and ERp5 reductase activities. Finally, molecular docking studies suggested myricetin formed non-covalent bonds with PDI and ERp5. CONCLUSIONS: PESc and its most abundant flavonoid myricetin strongly inhibit platelet function. Additionally, myricetin is a novel inhibitor of ERp5 and PDI, unveiling a new therapeutic perspective for the treatment of thrombotic disorders.
RESUMO
O cirurgião-dentista tem papel fundamental no diagnóstico precoce das leucemias, pois sinais ou sintomas podem ocorrer na boca, sendo mais comum nas fases agudas da doença, e mais frequentes na leucemia monocítica. A leucemia é uma doença que pode levar o paciente ao óbito em pouco tempo e os pacientes geralmente procuram o dentista acreditando serem doenças de origem local. O objetivo deste artigo é abordar as características odontológicas passíveis de identificação precoce da leucemia e discutir a responsabilidade ética e legal do cirurgião-dentista frente aos aspectos éticos e legais. Para tanto, foi realizado levantamento bibliográfico sobre a parte clínica do tema, bem como normativas e legislação correlatas. Conclui-se que é dever do cirurgião-dentista o conhecimento do diagnóstico de doenças e alterações que se manifestam na cavidade oral, bem como a correta interpretação do resultado de exames complementares, como o hemograma, pois este profissional pode responder legal e eticamente por falhas no diagnóstico e tratamento de pacientes com leucemia.
The dentist has a key role in the early diagnosis of leukemias, since signs or symptoms may occur in the mouth, being more common in the acute stages of the disease, and more frequent in monocytic leukemia. Leukemia is a disease that can take the patient to death in a short time and patients usually look for the dentist believing that they are diseases of local origin. The objective of this article is to discuss the dental characteristics that can be identified early in the leukemia and to discuss the ethical and legal responsibility of the dentist regarding ethical and legal aspects. For that, a review of literature was carried out on the clinical part of the topic, as well as normative and related legislation. It is concluded that it is the duty of the dentist to know the diagnosis of diseases and alterations that manifest in the oral cavity, as well as the correct interpretation of the result of complementary tests, such as the hemogram, since this professional can answer legally and ethically for failures in diagnosis and treatment of patients with leukemia.
