ZnO nanoparticles (ZnONPs) have been shown to have therapeutic potential in some diseases such as diabetes and cancer. However, concentration-dependent adverse effects have also been reported. Studies which evaluate the effects of ZnONPs on the cardiovascular system are scarce. This study aimed to evaluate the cardiovascular effects of a low dose of ZnONPs administered chronically in healthy rats. Changes in dyslipidemia biomarkers, blood pressure, aortic wall structure, vascular contractility, and expression of cannabinoid receptors in the aorta wall were evaluated. Healthy rats were divided into two groups: control or treated (one, two, and three months). The treated rats received an oral dose of 10 mg/kg/day. The results showed that treatment with ZnONPs induced dyslipidemia from the first month, increasing atherosclerosis risk, which was confirmed by presence of atherosclerotic alterations revealed by aorta histological analysis. In in vitro assays, ZnONPs modified the aorta contractile activity in response to the activation of cannabinoid receptors (CB1 and CB2). The expression of CB1 and CB2 was modified as well. Moreover, ZnONPs elicited an increase in blood pressure. In conclusion, long-time oral administration of ZnONPs induce dyslipidemia and atherosclerosis eliciting alterations in aorta contractility, CB1 and CB2 receptors expression, and an increase in blood pressure in healthy rats.
To better understand the mechanisms involved in the atherosclerosis progression, different models have been used. Currently there is no ideal model, each one has its advantages and disadvantages, especially when you want to study the disease progress. In this context we tested the hypothesis: the atherogenic “Paigen type” diet with modifications (APTDM), generates a stable model for the study of each phase of atherogenic process. Atherosclerosis was induced in 80 Wistar rats using APTDM consisting of 2 phases: 1) Hypervitamin, administered orally at a dose of 1.5 ml / kg / day for 12 days and 2) Hyperlipidic, administered for 48 days ad libitum . Experiments were carried out in 4 groups (n=16) with different doses (G1 = 75%, G2 = 50%, G3 = 33% and G4 = 25%) to obtain a dose-response curve, a healthy group (n=8; C) and a positive control (100% of the diet for 15 days; n=8; C+). Analysis was performed at day 15 for C+ and at day 30 (D30) and day 60 (D60) for the other groups. Aorta artery descending portion was extracted and histological analysis was performed to evaluate the atherosclerosis degree. Rats from C+ had severe grades (V-VII) at D15. All rats from G1 were sacrificed due to a poisoning for vitamin D2 excess. G2 rats were sacrificed at the end of D30 showing atherosclerotic lesions classified severe grades (V-VII). G3 showed mild degrees (I-III) at D30 and showed severe degrees (IV-VII) at D60. G4 showed mild degrees (I-III) at D30 and D60. Glucose, lipid profile, systolic (SBP) and diastolic (DBP) blood pressure was determined for G3. SBP decreased on D30 and D60 (123 ± 1 vs 109 ± 2 (p <0.01) and 124 ± 1 vs 99 ± 2 mmHg (p <0.01) respectively). Similar results in DBP were observed (83 ± 2 vs 69 ± 1 mmHg (p <0.01) at D60). Glucose increased on D30 and D60 (C = 98 ± 5 vs 159 ± 17 (p = 0.02) and 134 ± 4 mg/dL (p <0.01) respectively). Similar behavior for cholesterol (C = 56 ± 1 vs 114 ± 5 (p <0.01) and 128 ± 8 mg/dL (p <0.01) respectively), LDL (C = 39 ± 3 vs 103 ± 3 (p <0.01) and 123 ± 13 mg/dL (p <0.01) respectively) and triglycerides (C = 39 ± 2 vs 40 ± 1 (p = 0.01) and 74 ± 11 mg/dL (p = 0.01) respectively) was observed. HDL only increased on D60 (C = 22 ± 1 mg/dL vs 34 ± 3 (p <0.01)). In conclusion, APTDM to 33% (G3), generates a stable model for the study of the progress of each of the atherosclerosis phases in rats.
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