Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped NanosilverHolland NA1, Becak DP1, Jonathan H Shannahan2, Brown JM2, Carratt SA3, Winkle LSV3, Pinkerton KE3, Wang CM4, Munusamy P4, Don R Baer4, Sumner SJ5, Fennell TR5, Lust RM1 and Wingard CJ1*
- *Corresponding Author:
- Wingard CJ
Department of Physiology
Brody School of Medicine at East Carolina University
Greenville, North Carolina, USA
E-Mail: [email protected]
Received Date: August 27, 2015 Accepted Date: September 15, 2015 Published Date: October 01, 2015
Citation: Holland NA, Becak DP, Shannahan JH, Brown JM, Carratt SA, et al. (2015) Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver. J Nanomed Nanotechnol S6:006. doi:10.4172/2157-7439.S6-006
Copyright: © 2015 Holland NA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano-scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been reported to date. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of carbon-based nanomaterials. We hypothesized pulmonary exposure to Ag core AgNP induces a measureable increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and is associated with depressed coronary constrictor and relaxation responses. Secondarily, we addressed the potential contribution of silver ion release on AgNP toxicity.
Methods: Male Sprague-Dawley rats were exposed to 200 μl of 1 mg/ml of 20 nm citrate-capped Ag core AgNP, 0.01, 0.1, 1 mg/ml Silver Acetate (AgAc), or a citrate vehicle by intratracheal (IT) instillation. One and 7 days following IT instillation the lungs were evaluated for inflammation and the presence of silver; serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and coronary artery reactivity were assessed.
Results: AgNP instillation resulted in modest pulmonary inflammation with detection of silver in lung tissue and alveolar macrophages, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17α, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Silver within lung tissue was persistent at 7 days post IT instillation and was associated with an elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. AgAc resulted in a concentration dependent infarct expansion and depressed vascular reactivity without marked pulmonary inflammation or serum cytokine response.
Conclusions: Based on these data, IT instillation of AgNP increases circulating levels of several key cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.