Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury

Abstract

BackgroundThe uses of engineered nanomaterials have expanded in biomedical technology and consumer manufacturing. Furthermore, pulmonary exposure to various engineered nanomaterials has, likewise, demonstrated the ability to exacerbate cardiac ischemia reperfusion (I/R) injury. However, the influence of particle size or capping agent remains unclear. In an effort to address these influences we explored response to 2 different size gold core nanosilver particles (AgNP) with two different capping agents at 2 different time points. We hypothesized that a pulmonary exposure to AgNP induces cardiovascular toxicity influenced by inflammation and vascular dysfunction resulting in expansion of cardiac I/R Injury that is sensitive to particle size and the capping agent.MethodsMale Sprague–Dawley rats were exposed to 200 μg of 20 or 110 nm polyvinylprryolidone (PVP) or citrate capped AgNP. One and 7 days following intratracheal instillation serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and isolated coronary artery and aorta segment were assessed for constrictor responses and endothelial dependent relaxation and endothelial independent nitric oxide dependent relaxation.ResultsAgNP instillation resulted in modest increase in selected serum cytokines with elevations in IL-2, IL-18, and IL-6. Instillation resulted in a derangement of vascular responses to constrictors serotonin or phenylephrine, as well as endothelial dependent relaxations with acetylcholine or endothelial independent relaxations by sodium nitroprusside in a capping and size dependent manner. Exposure to both 20 and 110 nm AgNP resulted in exacerbation cardiac I/R injury 1 day following IT instillation independent of capping agent with 20 nm AgNP inducing marginally greater injury. Seven days following IT instillation the expansion of I/R injury persisted but the greatest injury was associated with exposure to 110 nm PVP capped AgNP resulted in nearly a two-fold larger infarct size compared to naïve.ConclusionsExposure to AgNP may result in vascular dysfunction, a potentially maladaptive sensitization of the immune system to respond to a secondary insult (e.g., cardiac I/R) which may drive expansion of I/R injury at 1 and 7 days following IT instillation where the extent of injury could be correlated with capping agents and AgNP size.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0159-z) contains supplementary material, which is available to authorized users.

The in Vitro Effect of Polyvinylpyrrolidone and Citrate Coated Silver Nanoparticles on Erythrocytic Oxidative Damage and Eryptosis

“…Our in vitro erythrocyte study is relevant to previous in vivo studies which demonstrated that exposure to AgNPs is associated with cardiovascular dysfunction in addition to cytotoxicity and oxidative stress [20,21]. We incubated the erythrocytes with vehicle or PVPor CT-AgNPs for 4 h; a time point similar to previous in vitro studies [18,31].…”

“…In addition, coating has been reported to play an important role in NPs toxicity. In this context, in vivo studies have reported that polyvinylpyrrolidone (PVP) and citrate (CT) coated AgNPs induce tissue specific toxicity and aggravate cardiac ischemic reperfusion injury [20,21]. Moreover, a previous in vitro study has shown that PVPand CT-AgNPs induce toxicity in J774A.1 macrophage and HT29 epithelial cells [22].…”

Ultrafine Particulate Matter Increases Cardiac Ischemia/Reperfusion Injury via Mitochondrial Permeability Transition Pore

“…These observations are congruent with previous experimental findings whereby exposure to PM alone induced minor or no observable changes in cardiac function. However, when PM exposure is paired to a secondary insult or stressor, PM is capable of exaggerating latent electrophysiological dysfunction (37) or worsening cardiac injury (25). Furthermore, it is possible that any changes associated with UFP induced modulation of ion channels leading to increased susceptibility to arrhythmogenesis would likely need greater than 24 hours to fully manifest (38).…”

“…Following the aspiration, the animal was returned to its cage and recovery was observed until normal grooming habits resumed. This form of oropharyngeal (OP) aspiration has been adopted by the members of the National Institute of Environmental Health Sciences Centers for Nanotechnology Health Implications Research (NCNHIR) and Nano GO consortiums in an efforts to minimize variability and is an accepted and previously published technique to achieve OP aspiration (25–27). …”

“…Areas were converted to weights by multiplying the mean of the AAR and IA of both sides of the slice by the weight of each slice. The total weight of the IA from all sections was then divided by the total weight of the AAR from all sections to obtain a percentage of the heart that was infarcted (25, 31, 32). …”