Abstract
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.
Highlights
Zinc oxide nanoparticles (ZnONPs) are being studied widely due to their multiple applications
Sixty rats were randomly divided into two experimental groups: control (n = 30) and treated with ZnO nanoparticles (ZnONPs) (10 mg/kg, n = 30), each group was subdivided into three groups (n = 10 per group) corresponding to one, two, and three months of treatment
ZnONPs decreased LDL-C concentration, an effect that was significant at the first (49%) and third month (26%) of the treatment compared to the control group
Summary
Zinc oxide nanoparticles (ZnONPs) are being studied widely due to their multiple applications. Nanomaterials 2021, 11, 2319 more research is needed to evaluate in detail their biological and toxicological effects in different tissues after long periods of administration. ZnONPs have been reported to release zinc ions capable of inducing oxidative stress and cell damage, generating a cytotoxic and genotoxic effect. There are studies that have evaluated the effects of ZnONPs on some organs or systems, the current knowledge is limited. Toxicity studies mainly at high doses of ZnONPs have shown accumulation of zinc in the liver, kidney, lung, heart, and spleen, inducing injury and in some cases death [8]. Other studies showed this type of effect was induced by ZnONPs, but dependent on the route of administration [9]. Hematological alterations, stomach, pancreas, and retina injuries have been reported [10] and, more recently, alterations in the nervous system [11,12]
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