Silver nanoparticles (AgNPs) have been studied worldwide for their potential biomedical applications. Specifically, they are proposed as a novel alternative for cancer treatment. However, the determination of their cytotoxic and genotoxic effects continues to limit their application. The commercially available silver nanoparticle Argovit™ has shown antineoplastic, antiviral, antibacterial, and tissue regenerative properties, activities triggered by its capacity to promote the overproduction of reactive oxygen species (ROS). Therefore, in this work, we evaluated the genotoxic and cytotoxic potential of the Argovit™ formulation (average size: 35 nm) on BALB/c mice using the micronucleus in a peripheral blood erythrocytes model. Besides, we evaluated the capability of AgNPs to modulate the genotoxic effect induced by cyclophosphamide (CP) after the administration of the oncologic agent. To achieve this, 5–6-week-old male mice with a mean weight of 20.11 ± 2.38 g were treated with water as negative control (Group 1), an single intraperitoneal dose of CP (50 mg/kg of body weight, Group 2), a daily oral dose of AgNPs (6 mg/kg of weight, Group 3) for three consecutive days, or a combination of these treatment schemes: one day of CP doses (50 mg/kg of body weight) followed by three doses of AgNPs (one dose per day, Group 4) and three alternate doses of CP and AgNPs (six days of exposure, Group 5). Blood samples were taken just before the first administration (0 h) and every 24 h for seven days. Our results show that Argovit™ AgNPs induced no significant cytotoxic or acute genotoxic damage. The observed cumulative genotoxic damage in this model could be caused by the accumulation of AgNPs due to administered consecutive doses. Furthermore, the administration of AgNPs after 24 h of CP seems to have a protective effect on bone marrow and reduces by up to 50% the acute genotoxic damage induced by CP. However, this protection is not enough to counteract several doses of CP. To our knowledge, this is the first time that the exceptional chemoprotective capacity produced by a non-cytotoxic silver nanoparticle formulation against CP genotoxic damage has been reported. These findings raise the possibility of using AgNPs as an adjuvant agent with current treatments, reducing adverse effects.
Polydactyly, hypopigmentation, and squamous cell carcinoma are common in cats. However, a cat exhibiting all of these conditions has not yet been reported. This study presents the case of a 14-year-old male Mexican cat, hypopigmented, with supernumerary fingers, two preaxial and one on each posterior limb, admitted to the clinic with a lesion in the left periocular region. The cat was subjected to a general physical examination, blood, and urine chemistry, as well as a biopsy and genomic instability assessment with an analysis of the red blood cells (RBC) micronucleated erythrocytes (RBC-MNE) in the peripheral blood. The biopsy was positive for squamous cell carcinoma, and the RBC-MNE count (8.6 MNE/1000 erythrocytes) was high compared to that previously described in other domestic cats or wild cats. Thus, the genomic instability of the RBC-MNE could be used as an indicator to identify clinical conditions of felines, particularly those with one of the characteristics exhibited by this Mexican cat. The RBC-MNE test is the most widely used in the world for the evaluation of DNA damage, but to our knowledge, it has not been used to identify vulnerable non-human specimens.
El estudio de la genotoxicidad en modelos murinos es útil para responder las dudas relacionadas con la seguridad por el uso de nanomateriales, sobre todo cuando se pretende el desarrollo de nuevas opciones terapéuticas. El propósito de este trabajo fue evaluar la capacidad genotóxica de AgNPs Argovit™ a partir de la técnica de micronúcleos en reticulocitos de sangre periférica de ratones, prueba ampliamente utilizada para conocer el potencial genotóxico de diferentes agentes. Las nanopartículas de plata se suministraron en dosis terapéuticas por vía oral (indicadas para perros como tratamiento para el moquillo) durante tres días a un grupo conformado por siete ratones y a otros dos grupos con igual número de ratones se administró respectivamente agua inyectable y arabinosa C. Los especímenes fueron medidos, pesados antes y después del experimento. También se tomaron diariamente muestras de sangre periférica mediante un corte en la punta de la cola para posteriormente realizar extendidos sobre portaobjetos para la prueba de micronúcleos en reticulocitos. Los frotis se fijaron en etanol al 80 % y se tiñeron con anaranjado de acridina para posteriormente leer en 1000 reticulocitos la presencia de micronúcleos con microscopio de fluorescencia. Los resultados preliminares muestran diferencias significativas en el número de micronúcleos en reticulocitos entre los tres grupos, por lo que se requiere comprobar este resultado con otro tipo de modelos in vitro.
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