TY - JOUR

T1 - Role of oxidative stress in carbon nanotube-generated health effects

AU - Møller, Peter

AU - Christophersen, Daniel Vest

AU - Jensen, Ditte Marie

AU - Kermanizadeh, Ali

AU - Roursgaard, Martin

AU - Jacobsen, Nicklas Raun

AU - Hemmingsen, Jette Gjerke

AU - Danielsen, Pernille Høgh

AU - Cao, Yi

AU - Jantzen, Kim

AU - Klingberg, Henrik

AU - Hersoug, Lars-Georg

AU - Loft, Steffen

PY - 2014/11

Y1 - 2014/11

N2 - 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.

AB - 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.

KW - Animals

KW - Antioxidants/metabolism

KW - Cardiovascular Diseases/chemically induced

KW - DNA Damage/drug effects

KW - Humans

KW - Inflammation/chemically induced

KW - Lipid Peroxidation/drug effects

KW - Lung Diseases/chemically induced

KW - Nanotechnology

KW - Nanotubes, Carbon/toxicity

KW - Oxidative Stress/drug effects

KW - Reactive Oxygen Species/metabolism

U2 - 10.1007/s00204-014-1356-x

DO - 10.1007/s00204-014-1356-x

M3 - Review article

C2 - 25212906

VL - 88

SP - 1939

EP - 1964

JO - Archives of toxicology

JF - Archives of toxicology

SN - 0340-5761

IS - 11

ER -