Modest vasomotor dysfunction induced by low doses of C60 fullerenes in apolipoprotein E knockout mice with different degree of atherosclerosis

BackgroundExposure to small size particulate matter in urban air is regarded as a risk factor for cardiovascular effects, whereas there is little information about the impact on the cardiovascular system by exposure to pure carbonaceous materials in the nano-size range. C60 fullerenes are nano-sized particles that are expected to have a widespread use, including cosmetics and medicines.MethodsWe investigated the association between intraperitoneal injection of pristine C60 fullerenes and vasomotor dysfunction in the aorta of 11–13 and 40–42 weeks old apolipoprotein E knockout mice (apoE-/-) with different degree of atherosclerosis.ResultsThe aged apoE-/-mice had lower endothelium-dependent vasorelaxation elicited by acetylcholine in aorta segments mounted in myographs and the phenylephrine-dependent vasoconstriction response was increased. One hour after an intraperitoneal injection of 0.05 or 0.5 mg/kg of C60 fullerenes, the young apoE-/- mice had slightly reduced maximal endothelium-dependent vasorelaxation. A similar tendency was observed in the old apoE-/- mice. Hampered endothelium-independent vasorelaxation was also observed as slightly increased EC50 of sodium nitroprusside-induced vasorelaxation response in young apoE-/- mice.ConclusionTreatment with C60 fullerenes affected mainly the response to vasorelaxation in young apoE-/- mice, whereas the vasomotor dysfunction in old apoE-/- mice with more advanced atherosclerosis was less affected by acute C60 fullerene treatment. These findings represent an important step in the hazard characterization of C60 fullerenes by showing that intraperitoneal administration is associated with a moderate decrease in the vascular function of mice with atherosclerosis.

[1]  C. Teng,et al.  Effect of Hexasulfobutylated C60 on the Isolated Aortic Ring of Guinea Pig , 2002, Pharmacology.

[2]  T. Sandström,et al.  Air Pollution and Atherothrombosis , 2007, Inhalation toxicology.

[3]  W. Cascio,et al.  Ultrafine particulate matter exposure augments ischemia reperfusion injury in mice , 2006, American journal of physiology. Heart and circulatory physiology.

[4]  Thomas Sandström,et al.  Persistent endothelial dysfunction in humans after diesel exhaust inhalation. , 2007, American journal of respiratory and critical care medicine.

[5]  Inhibition of nitric oxide synthase isoforms by tris-malonyl-C(60)-fullerene adducts. , 2000, Archives of biochemistry and biophysics.

[6]  P. Borm,et al.  Vascular effects of ambient particulate matter instillation in spontaneous hypertensive rats. , 2004, Toxicology and applied pharmacology.

[7]  David E Newby,et al.  Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis , 2005, Circulation.

[8]  G. Baker,et al.  Inhalation toxicity and lung toxicokinetics of C60 fullerene nanoparticles and microparticles. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  P. Møller,et al.  Diesel exhaust particles induce endothelial dysfunction in apoE-/- mice. , 2007, Toxicology and applied pharmacology.

[10]  T. Mashino,et al.  Inhibitory effect of a fullerene derivative, monomalonic acid C60, on nitric oxide-dependent relaxation of aortic smooth muscle. , 1997, General pharmacology.

[11]  S. Goldman,et al.  Oxidative stress contributes to vascular endothelial dysfunction in heart failure. , 2001, American journal of physiology. Heart and circulatory physiology.

[12]  Roel P F Schins,et al.  Inhaled particles and lung cancer. Part A: Mechanisms , 2004, International journal of cancer.

[13]  Magnus Svartengren,et al.  No Significant Translocation of Inhaled 35-nm Carbon Particles to the Circulation in Humans , 2006, Inhalation toxicology.

[14]  Nicklas Raun Jacobsen,et al.  Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice , 2009, Particle and Fibre Toxicology.

[15]  Stephen R. Wilson,et al.  [60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. , 2005, Nano letters.

[16]  Vincent Castranova,et al.  Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction , 2008, Particle and Fibre Toxicology.

[17]  R. Céolin,et al.  Early effects of C60 Administration in Swiss Mice: A Preliminary Account for In Vivo C60 Toxicity. , 1996 .

[18]  J. Hogg,et al.  Particulate air pollution induces progression of atherosclerosis. , 2002, Journal of the American College of Cardiology.

[19]  T. Sandström,et al.  Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. , 2007, The New England journal of medicine.

[20]  W G Kreyling,et al.  Long-Term Clearance Kinetics of Inhaled Ultrafine Insoluble Iridium Particles from the Rat Lung, Including Transient Translocation into Secondary Organs , 2004, Inhalation toxicology.

[21]  N. Iwai,et al.  Nanomaterials induce oxidized low-density lipoprotein cellular uptake in macrophages and platelet aggregation. , 2007, Circulation journal : official journal of the Japanese Circulation Society.

[22]  Antonio Marcomini,et al.  Genotoxicity, cytotoxicity, and reactive oxygen species induced by single‐walled carbon nanotubes and C60 fullerenes in the FE1‐Muta™Mouse lung epithelial cells , 2008, Environmental and molecular mutagenesis.

[23]  W. Kreyling,et al.  TRANSLOCATION OF ULTRAFINE INSOLUBLE IRIDIUM PARTICLES FROM LUNG EPITHELIUM TO EXTRAPULMONARY ORGANS IS SIZE DEPENDENT BUT VERY LOW , 2002, Journal of toxicology and environmental health. Part A.

[24]  T. Mashino,et al.  Inhibitory effects of a fullerene derivative, dimalonic acid C60, on nitric oxide-induced relaxation of rabbit aorta. , 1997, European journal of pharmacology.

[25]  P. Møller,et al.  Oxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles. , 2007, Toxicology.

[26]  Frances Silverman,et al.  Inhalation of Fine Particulate Air Pollution and Ozone Causes Acute Arterial Vasoconstriction in Healthy Adults , 2002, Circulation.

[27]  W. Kreyling,et al.  The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung , 2005, Particle and Fibre Toxicology.

[28]  Tadashi Suzuki,et al.  Involvement of free radicals followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: comparison of the therapeutic potential of fullerene, mepacrine, and cooling. , 2007, Toxicology.

[29]  Steffen Loft,et al.  Oxidative stress-induced DNA damage by particulate air pollution. , 2005, Mutation research.

[30]  D. J. Wolff,et al.  Inhibition of Nitric Oxide Synthase Isoforms by Tris-Malonyl-C60-Fullerene Adducts , 2000 .

[31]  Lung-Chi Chen,et al.  Effects of Subchronic Exposures to Concentrated Ambient Particles (CAPs) in Mice: V. CAPs Exacerbate Aortic Plaque Development in Hyperlipidemic Mice , 2005, Inhalation toxicology.

[32]  Alireza Afshari,et al.  Indoor particles affect vascular function in the aged: an air filtration-based intervention study. , 2008, American journal of respiratory and critical care medicine.

[33]  Constantinos Sioutas,et al.  Potential Role of Ultrafine Particles in Associations between Airborne Particle Mass and Cardiovascular Health , 2005, Environmental health perspectives.

[34]  Toshinori Murayama,et al.  Nano-sized carbon black exposure exacerbates atherosclerosis in LDL-receptor knockout mice. , 2007, Circulation journal : official journal of the Japanese Circulation Society.

[35]  Keld Alstrup Jensen,et al.  In vivo biology and toxicology of fullerenes and their derivatives. , 2008, Basic & clinical pharmacology & toxicology.

[36]  Kent E. Pinkerton,et al.  Meeting Report: Hazard Assessment for Nanoparticles—Report from an Interdisciplinary Workshop , 2007, Environmental health perspectives.

[37]  A. Herman,et al.  Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI. , 2003, Cardiovascular research.

[38]  V. Fuster,et al.  Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. , 2005, JAMA.

[39]  Steffen Loft,et al.  Air pollution, oxidative damage to DNA, and carcinogenesis. , 2008, Cancer letters.

[40]  G. Hansson,et al.  Effects of sex and age on atherosclerosis and autoimmunity in apoE-deficient mice. , 1999, Atherosclerosis.

[41]  R. M. Arruda,et al.  Evaluation of Vascular Function in Apolipoprotein E Knockout Mice With Angiotensin-Dependent Renovascular Hypertension , 2005, Hypertension.

[42]  Vincent Castranova,et al.  Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases , 2007, Particle and Fibre Toxicology.

[43]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[44]  J. Hogg,et al.  Exposure to ambient particles accelerates monocyte release from bone marrow in atherosclerotic rabbits. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[45]  Anna Shvedova,et al.  Cardiovascular Effects of Pulmonary Exposure to Single-Wall Carbon Nanotubes , 2006, Environmental health perspectives.

[46]  Leslie A. Smith,et al.  Mechanism of Endothelial Dysfunction in Apolipoprotein E-Deficient Mice , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[47]  R. Kulka,et al.  Particulate air pollution and vascular reactivity: the bus stop study , 2007, International archives of occupational and environmental health.