Avaliação dos efeitos do resveratrol em parâmetros do sistema purinérgico e biomarcadores oxidativos em plaquetas e soro de ratos com hipotireoidismo

Abstract

Hypothyroidism is an endocrine disorder characterized by low production of thyroid hormones and is frequently observed in the population, with a higher prevalence in females. It is associated with an increased cardiovascular risk, which may be influenced by platelet aggregation and oxidative stress. Despite hormonal replacement therapy, many patients continue to experience persistent symptoms, sparking interest in finding complementary therapies, and polyphenols such as resveratrol have emerged as potential candidates due to their numerous beneficial properties for the body. Several studies have been conducted to improve the understanding of the underlying mechanisms of this disease, with a focus on the purinergic system and oxidative stress biomarkers. Research has consistently demonstrated that alterations in these pathways can influence platelet changes, leading to increased aggregation and consequently raising cardiovascular risk in the context of hypothyroidism. In light of this, the present study aimed to investigate the effects of resveratrol on platelets and serum of rats with hypothyroidism, evaluating its effects on the density of the platelet receptor P2Y12, the activity and density of purinergic enzymes, and oxidative parameters. Hypothyroidism was induced by methimazole in the experimental groups (MMI/S, MMI/RSV), and resveratrol was administered as a preventive therapy (MMI/RSV) for 30 days, with seven animals per group. The results showed that animals with hypothyroidism exhibited a reduction in the activity of NTPDase and 5’- Nucleotidase enzymes, while resveratrol maintained adenosine triphosphate (ATP) hydrolysis close to control group levels, and prevented the increase in Adenosine deaminase/CD46 enzyme activity and density, which were altered by hypothyroidism. Additionally, resveratrol significantly reduced the density of the P2Y12 receptor in platelets. Hypothyroidism caused oxidative stress, evidenced by redox imbalance, but resveratrol effectively prevented the increase of reactive species (RS) and thiobarbituric acid reactive substances (TBARS), and restored antioxidant levels such as glutathione-S-transferase (GST) activity and total thiol (T-SH) levels, which were reduced in the MMI/S group. These results suggest that resveratrol may modulate purinergic enzymes, reduce the density of the P2Y12 receptor, and exert antioxidant effects in hypothyroidism, providing potential mechanisms for cardiovascular protection. These findings contribute to the understanding of the mechanisms involved in hypothyroidism and may pave the way for the development of complementary therapeutic approaches aiming at a more effective treatment of this endocrine disorder. However, further investigations are required to explore and better understand these mechanisms, as well as to assess the combination of resveratrol with existing maintenance therapies.