ABSTRACT
With the increasing applications of silver nanoparticles (Ag NPs), the concerns of widespread human exposure as well as subsequent health risks have been continuously growing. The acute and chronic toxicities of Ag NPs in cellular tests and animal tests have been widely investigated. Accumulating evidence shows that Ag NPs can induce inflammation, yet the overall mechanism is incomplete. Herein, using gold nanorod core/silver shell nanostructures (Au@Ag NRs) as a model system, we studied the influence on mice liver and lungs from the viewpoint of metabolism. In agreement with previous studies, Au@Ag NRs' intravenous exposure caused inflammatory reaction, accompanying with metabolic alterations, including energy metabolism, membrane/choline metabolism, redox metabolism, and purine metabolism, the disturbances of which contribute to inflammation. At the same time, dopamine metabolism in liver was also changed. This is the first time to observe the production of dopamine in non-neural tissue after treatment with Ag NPs. As the upregulation of dopamine resists inflammation, it indicates the activation of antioxidant defense systems against oxidative stress induced by Au@Ag NRs. In the end, our findings deepened the understanding of molecular mechanisms of Ag NPs-induced inflammation and provide assistance in the rational design of their biomedical applications.
Subject(s)
Dopamine/metabolism , Inflammation/drug therapy , Nanostructures/chemistry , Nanotubes/chemistry , Animals , Gold/chemistry , Humans , Inflammation/metabolism , Inflammation/pathology , Liver/drug effects , Lung/drug effects , Metabolism/drug effects , Metal Nanoparticles/chemistry , Mice , Nanostructures/administration & dosage , Oxidative Stress/drug effects , Silver/chemistryABSTRACT
Effective and quick screening and cardiotoxicity assessment are very crucial for drug development. Here, a novel composite hydrogel composed of carbon fibers (CFs) with high conductivity and modulus with polyvinyl alcohol (PVA) is reported. The conductivity of the composite hydrogel PVA/CFs is similar to that of natural heart tissue, and the elastic modulus is close to that of natural heart tissue during systole, due to the incorporation of CFs. PVA/CFs remarkably enhance the maturation of neonatal rat cardiomyocytes (NRCM) in vitro by upregulating the expression of α-actinin, troponin T, and connexin-43, activating the signaling pathway of α5 and ß1 integrin-dependent ILK/p-AKT, and increasing the level of RhoA and hypoxia-inducible factor-1α. As a result, the engineered cell sheet-like constructs NRCM@PVA/CFs display much more synchronous, stable, and robust beating behavior than NRCM@PVA. When exposed to doxorubicin or isoprenaline, NRCM@PVA/CFs can retain effective beating for much longer time or change the contractile rate much faster than NRCM@PVA, respectively, therefore representing a promising heart-like platform for in vitro drug screening and cardiotoxicity assessment.
