Role of oxidative stress in carbon nanotube-generated health effects

Abstract

The development of products containing carbon nanotubes (CNTs) is a major achievement of nanotechnology, although concerns regarding risk of toxic effects linger if the hazards associated with these materials are not thoroughly investigated. Exposure to CNTs has been associated with depletion of antioxidants, increased intracellular production of reactive oxygen species and pro-inflammatory signaling in cultured cells with primary function in the immune system as well as epithelial, endothelial and stromal cells. Pre-treatment with antioxidants has been shown to attenuate these effects, indicating a dependency of oxidative stress on cellular responses to CNT exposure. CNT-mediated oxidative stress in cell cultures has been associated with elevated levels of lipid peroxidation products and oxidatively damaged DNA. Investigations of oxidative stress endpoints in animal studies have utilized pulmonary, gastrointestinal, intravenous and intraperitoneal exposure routes, documenting elevated levels of lipid peroxidation products and oxidatively damaged DNA nucleobases especially in the lungs and liver, which to some extent occur concomitantly with altered levels of components in the antioxidant defense system (glutathione, superoxide dismutase or catalase). CNTs are biopersistent high aspect ratio materials, and some are rigid with lengths that lead to frustrated phagocytosis and pleural accumulation. There is accumulating evidence showing that pulmonary exposure to CNTs is associated with fibrosis and neoplastic changes in the lungs, and cardiovascular disease. As oxidative stress and inflammation responses are implicated in the development of these diseases, converging lines of evidence indicate that exposure to CNTs is associated with increased risk of cardiopulmonary diseases through generation of a pro-inflammatory and pro-oxidant milieu in the lungs.

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

“…Rigid needle-like ENM can also cause phagocyte death by literally perforating the cell membrane (102).…”

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

“…69,70 Exposure to CNT resulted in adverse effects in various cell types in vitro, including those with immune-related functions, such as macrophages (mφ) (rat alveolar mφ [NR8383] and THP1-derived mφ), human microvascular endothelial cells, human epidermal keratinocytes, human bronchial epithelial (BEAS-2B), human mesothelial (MeT-5A) cells, and lymphoblastoid (MCL-5) cells. 71 In vivo studies have shown depletion of antioxidants, increased intracellular production of ROS, and proinflammatory signaling, resulting in fibrosis and neoplastic changes in the lungs of mice and rats and elevated risk of cardiopulmonary diseases by generation of a proinflammatory and prooxidant milieu in the lungs. 71 For nanosilver, immunosuppression was observed after 28-day repeated dose intravenous administration to Wistar rats, 72,73 although no immunotoxicity was observed in another study using oral administration.…”

“…71 In vivo studies have shown depletion of antioxidants, increased intracellular production of ROS, and proinflammatory signaling, resulting in fibrosis and neoplastic changes in the lungs of mice and rats and elevated risk of cardiopulmonary diseases by generation of a proinflammatory and prooxidant milieu in the lungs. 71 For nanosilver, immunosuppression was observed after 28-day repeated dose intravenous administration to Wistar rats, 72,73 although no immunotoxicity was observed in another study using oral administration. 74 Some NMs can interact with the immune system in a direct way through toll-like receptors (TLRs).…”

Highlight report: redox—metals in toxicology

“…In particular, research on oxidative stress induced by nanosized materials has become more and more important in recent years (Møller et al 2014;Zhang et al 2015;Bondarenko et al 2013). Moreover, the relatively high exposure of humans to some heavy metals (Hengstler et al 2003;King et al 2015;Jaishankar et al 2014;Tom and Fletcher 2014;Shiue and Hristova 2014;Pizzino et al 2014;Jung et al 2003) has motivated intensive research on metal toxicity, including nickel-induced DNA damage (Yao and Costa 2014), manganese-induced neurotoxicity (Krishna et al 2014;Kumasaka et al 2014), and lead-associated mimicry of essential minerals and immunotoxicity (Breton et al 2013;Jorissen et al 2013).…”