Nanotoxicology: characterization, dosing and health effects. Monteiro-Riviere NA, Tran CL, eds. New York: Informa Healthcare, 2007 Jul; :237-246
Overall, these initial studies demonstrate that respiratory exposure to high concentrations, mostly agglomerated, SWCNTs provokes not only pulmonary toxicity but vascular effects related to mitochondrial oxidative modifications and accelerated atheroma formation. Pulmonary exposure to SWCNT may induce cardiovascular effects either directly or indirectly through mitochondrial oxidative perturbations, which can result in altered vessel homeostasis. It is possible that individual SWCNTs can translocate from the lung into the systemic circulation causing direct cardiovascular endothelial damage. It has been reported that nanoparticles treated with albumin and/or surfactant proteins cross the alveolocapillary barrier to gain access to the systemic circulation (30.31). The proximity between epithelial type I and endothelial cell caveolar membrane structures might play a role in the particle translocation mechanisms (32). Since the SWCNT are not well recognized and cleared by lung macrophages (9.33), nanotubes, dispersed or disintegrated from the agglomerates, may persist in the alveolar space, which will facilitate their access into the systemic circulation. Behavior and fate of SWCNTs have been addressed only in several pharmacokinetic studies evaluating the body distribution of the material after injection for the purposes of biomedical application development (34,35). These studies applied water-soluble SWCNTs (functionalized in the first two or covered with an artificial surfactant in the last reference) and did not find acute toxicity or adverse reactions. The SWCNTs have been traced by linking them covalently or noncovalently to external fluorophores or chelated radioisotopes (34). Cherukuri et al. (35) applied near-infrared fluorescence technique to monitor SWCNT with sensitivity high enough to detect a single intracellular nanotube. This method might find an application for evaluation of SWCNT distribution in the experimental settings simulating occupational paradigm of exposure and to provide insights the partition of single tubes from the lung into the systemic circulation. Indirect processes are also possible to play a role in the cardiovascular effects induced by SWCNT exposure. Increased circulating cytokine levels (e.g., IL-6, IL-, IL-lBeta , GM-CSF) have been found in humans with pulmonary inflammation due to chronic obstructive pulmonary disease (COPD), asbestos, zinc oxide, particulate matter exposure, and endotoxin. (36-38). Although SWCNT exposure was associated with atherosclerosis acceleration, significant differences in the plasma levels of IL-6, IL-10, MCP-l, TNF-alpha, and IFN-gamma were not observed although more acute effects cannot be ruled out (24). Unpurified SWCNTs are deposited in the lung, chronic inflammation in the lung as well as systemic circulation might be triggered. In addition to low inflammation, recently it has been suggested that inefficient metabolism in blood vessels as a result of ischemic events can cause vascular diseases through mitochondrial dysfunction (39). Mediators, released from the lung into the systemic circulation or ischemic events, associated with altered pulmonary function seen after SWCNT exposure may lead to vascular-oxidative modifications.