Name: JÚLIA ANTONIETTA DANTAS DA SILVA

Publication date: 19/04/2024

Examining board:

Namesort descending Role
ALESSANDRA SIMAO PADILHA Examinador Interno
ITALLA MARIA PINHEIRO BEZERRA Examinador Externo

Summary: Introduction: Individuals with diabetes, in addition to having a higher risk of
developing cardiovascular diseases, also exhibit an imbalance in copper metabolism.
Copper is an essential metal that, under conditions of exposure, can also trigger
cardiovascular alterations. Objective: the purpose of this study is to investigate the
effect of chronic exposure to twice the recommended daily dose of CuCl2 on vascular
reactivity in isolated thoracic aorta segments of diabetic and non-diabetic rats.
Methods: 80 Wistar rats, aged 12 weeks, were divided into four groups: Control (Ct),
Copper (Cu), Diabetes Mellitus (DM), and Diabetes + Copper (DM+Cu). Type 1
diabetes was induced using streptozotocin (65mg/kg i.p), and the animals exposed to
copper received twice the recommended daily dose (25.7g/Kg/day CuCl2) for 30
days. After treatment, the vascular reactivity of aortic rings was assessed. Samples of
aortas and perivascular adipose tissue (PVAT) were stored for histological evaluations,
presence of O2•, H2O2, NO, and pro-inflammatory factors. Results: The main
findings of this study demonstrated that the DM+Cu group had a pronounced weight
loss, associated with a higher hyperglycemic state than the DM group, in addition to
an increase in pro-inflammatory factors in PVAT (IL-6 and TNF-). We observed a
reduction in vascular reactivity to phenylephrine in the absence of PVAT associated
with an increase in vasodilator factors: NO and H2O2. The involvement of K+

channels
and AT1 receptors was also detected, and an increase in vascular reactivity in the
absence of the endothelium. Additionally, we observed an increase in the thickness of
the aorta wall, greater collagen deposition, and an enhanced endothelium-dependent
and -independent relaxation when compared to the DM group. In the presence of
PVAT, there was an increase in vascular reactivity to phenylephrine in the DM+Cu and
Cu groups. Conclusion: These findings demonstrate that exposure to twice the
recommended daily dose of copper, in diabetic animals leads to endothelial and
perivascular adipose tissue dysfunction, associated with an increase in vasodilator and
pro-inflammatory factors.

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