ZnO Nanoparticles Induce Dyslipidemia and Atherosclerotic Lesions Leading to Changes in Vascular Contractility and Cannabinoid Receptors Expression as Well as Increased Blood Pressure
Adriana Ceballos-Gutiérrez,
Alejandrina Rodríguez-Hernández,
María del Rosario Álvarez-Valadez,
Saraí Limón-Miranda,
Felipa Andrade,
Alejandro Figueroa-Gutiérrez,
Irene Díaz-Reval,
Alejandro Apolinar-Iribe,
Luis Castro-Sánchez,
Javier Alamilla,
Enrique Sánchez-Pastor,
Adolfo Virgen-Ortiz
Affiliations
Adriana Ceballos-Gutiérrez
Facultad de Medicina, Universidad de Colima, Colima 28040, Mexico
Alejandrina Rodríguez-Hernández
Facultad de Medicina, Universidad de Colima, Colima 28040, Mexico
María del Rosario Álvarez-Valadez
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima 28045, Mexico
Saraí Limón-Miranda
Departamento de Ciencias Químico Biológicas y Agropecuarias, Unidad Regional Sur, Universidad de Sonora, Navojoa 85880, Mexico
Felipa Andrade
Institito Tecnológico de Colima, Colima 28076, Mexico
Alejandro Figueroa-Gutiérrez
Facultad de Medicina, Universidad de Colima, Colima 28040, Mexico
Irene Díaz-Reval
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima 28045, Mexico
Alejandro Apolinar-Iribe
Departamento de Física, Unidad Centro, Universidad de Sonora, Hermosillo 83000, Mexico
Luis Castro-Sánchez
Centro Universitario de Investigaciones Biomédicas, CONACYT-Universidad de Colima, Universidad de Colima, Colima 28045, Mexico
Javier Alamilla
Centro Universitario de Investigaciones Biomédicas, CONACYT-Universidad de Colima, Universidad de Colima, Colima 28045, Mexico
Enrique Sánchez-Pastor
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima 28045, Mexico
Adolfo Virgen-Ortiz
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima 28045, Mexico
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.