C60 Exposure Augments Cardiac Ischemia/Reperfusion Injury and Coronary Artery Contraction in Sprague Dawley Rats

Abstract

The potential uses of engineered C₆₀ fullerene (C₆₀) have expanded in recent decades to include industrial and biomedical applications. Based on clinical findings associated with particulate matter exposure and our data with multi-walled carbon nanotubes, we hypothesized that ischemia/reperfusion (I/R) injury and pharmacological responses in isolated coronary arteries would depend upon the route of exposure and gender in rats instilled with C₆₀. Male and female Sprague Dawley rats were used to test this hypothesis by surgical induction of cardiac I/R injury in situ 24 h after intratracheal (IT) or intravenous (IV) instillation of 28 μg of C₆₀ formulated in polyvinylpyrrolidone (PVP) or PVP vehicle. Serum was collected for quantification of various cytokines. Coronary artery segments were isolated for assessment of vasoactive pharmacology via wire myography. Both IV and IT exposure to C₆₀ resulted in expansion of myocardial infarction in male and female rats following I/R injury. Serum-collected post-I/R showed elevated concentrations of interleukin-6 and monocyte chemotactic protein-1 in male rats exposed to IV C₆₀. Coronary arteries isolated from male rats exposed to IT C₆₀ demonstrated augmented vasocontraction in response to endothelin-1 that was attenuated with Indomethacin. IV C₆₀ exposure resulted in impaired acetylcholine relaxation in male rats and IT C₆₀ exposure resulted in depressed vasorelaxation in response to sodium nitroprusside in female rats. Based on these data, we conclude that IT and IV exposure to C₆₀ results in unique cardiovascular consequences that may favor heightened coronary resistance and myocardial susceptibility to I/R injury.

Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver

“…Interestingly, we found that IT exposure to AgNP resulted in a depressed serotonin constrictor stress response. This finding contrasts other reports of IT exposure to various nanomaterials associated with augmented vascular constrictor responses [18,42,43] and elevated mean arterial pressure [10]. We observed that IT instillation of citrate may also have vasoactive properties as stress generation to 5-HT was further reduced compared to coronary artery segment responses from naïve or AgNP instilled rats.…”

“…These findings are congruent with other studies that have investigated the potential for a negative cardiovascular impact following pulmonary exposures to various nanomaterials [15,18,22]. One hypothesis proposes that the pulmonary instillation of a nanomaterial establishes a pro-inflammatory condition that primes the target organ for exacerbation of an evoked injury response such as cardiac I/R.…”

“…Isolation of the coronary artery was performed as previously described [18]. The heart was excised and placed in ice-cold physiological saline solution (PSS); [mM] 140.0 NaCl, 5.0 KCl, 1.6 CaCl 2 , 1.2 MgSO 4 , 1.2 3-[N-morpholino]-propane sulfonic acid, 5.6 D-glucose, and 0.02 EDTA (pH 7.4 @ 37°C).…”

Safe Handling of Engineered Nanomaterials: Turning Knowledge Into Practice

“…* In fact, the nanotechnology projects listed in Appendix C show how these projects range from development applications with clear societal and commercial benefits (i.e., nanofiber-based volatile organic compound sensors, ceramic nanoparticles for next generation dental composites) 18,19 to those that focus on better understanding their potential impacts on health and the environment (i.e., Nanomaterial Registry, toxicity laboratory studies involving C 60 , risk analysis and decision support). 20, 21 In these diverse research projects, discussions of the potential hazards, risks, and uncertainties related to ENMs are integrated naturally, and many of the projects funded by US regulatory agencies such as NIH and the Environmental Protection Agency are designed to support a more proactive approach to developing nanotechnologies and ENMs. Finally, by creating an internal health and safety team dedicated to establishing, monitoring, and conducting workplace safety protocols, RTI can document the effectiveness of various safety controls alongside standard workplace practices.…”

Nanotoxicology: Contemporary Issues and Future Directions

“…Intravenous administration of fullerene resulted in increased serum interleukin-6 and monocyte chemotactic protein-1. Based on these observations, it was concluded that intratracheal and intravenous exposure of C60 results in unique cardiovascular consequences that may favor heightened coronary resistance and myocardial susceptibility to ischemia reperfusion injury [ 208 ]. In an air pouch model of acute infl ammation, fullerene alone did not induce any kind of infl ammation and proinfl ammatory cytokine release; however, fullerene can act in concert with other agents to cause infl ammation; in the presence of lipopolysaccharides (LPS) fullerene increased the local production of several cytokines/chemokines, similar type of situation that is likely to occur in vivo [ 209 ].…”