Effect of titanium dioxide on the oxidative metabolism of alveolar macrophages: an experimental study in rats.

Metallic implants of titanium are used therapeutically in biomedicine because of its excellent biocompatibility. However, no metal or alloy is completely inert. We have previously shown that titanium oxide (TiO(2)) is transported in blood by phagocytic monocytes and deposited in organs such as liver, spleen, and lung 6 months after intraperitoneal injection (ip). Furthermore, it is well known that exposure to metal traces alters the cellular redox status. Thus, the aim of the present study was to determine the presence of titanium in target organs after chronic exposure, assess the potential structural alterations, and evaluate the oxidative metabolism of alveolar macrophages (AM) in the lung. Rats were ip injected with 1.60 g/100 g body wt of TiO(2) in saline solution. Organs (liver, spleen, lung) were processed for histological evaluation. Reactive oxygen species (ROS) in AM obtained by bronchoalveolar lavage (BAL) were evaluated using the nitroblue tetrazolium test and quantitative evaluation by digital image analysis. The histological analysis of organs revealed the presence of titanium in the parenchyma of these organs with no associated tissue damage. Although in lung alveolar macrophages TiO(2) induced a significant rise in ROS generation, it failed to cause tissue alteration. This finding may be attributed to an adaptive response.

[1]  L. Sennerby On the bone tissue response to titanium implants , 1991 .

[2]  B. Molinari,et al.  Role of distinct subpopulations of peritoneal macrophages in the regulation of reactive oxygen species release. , 1999, Free radical biology & medicine.

[3]  I Herrmann,et al.  Osseointegrated implants for treatment of partially edentulous jaws: A 5 year prospective multicentre study , 1994 .

[4]  J. Paulauskis,et al.  Mediating phosphorylation events in the vanadium-induced respiratory burst of alveolar macrophages. , 1999, Toxicology and applied pharmacology.

[5]  A. Ferguson,et al.  Tissue reaction in rabbit muscle exposed to metallic implants. , 1967, Journal of biomedical materials research.

[6]  A. Ferguson,et al.  The ionization of metal implants in living tissues. , 1960, The Journal of bone and joint surgery. American volume.

[7]  R. Leggett,et al.  The behavior and chemical toxicity of U in the kidney: a reassessment. , 1989, Health physics.

[8]  S. Steinemann Titanium--the material of choice? , 1998, Periodontology 2000.

[9]  M. De la Fuente,et al.  Changes in the superoxide production and other macrophage functions could be related to the mortality of mice with endotoxin-induced oxidative stress. , 2003, Physiological research.

[10]  K. P. Lee,et al.  Pulmonary response to impaired lung clearance in rats following excessive TiO2 dust deposition. , 1986, Environmental research.

[11]  P. Branemark,et al.  Osseointegrated implants in the treatment of the edentulous jaw. Experience from a 10-year period. , 1977, Scandinavian journal of plastic and reconstructive surgery. Supplementum.

[12]  S. Peddada,et al.  The role of oxidative stress in indium phosphide-induced lung carcinogenesis in rats. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  J. Ferin,et al.  Biological effects and toxicity assessment of titanium dioxides: anatase and rutile. , 1985, American Industrial Hygiene Association journal.

[14]  Qamar Rahman,et al.  Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. , 2002, Environmental health perspectives.

[15]  T Albrektsson,et al.  A multicenter report on osseointegrated oral implants. , 1988, The Journal of prosthetic dentistry.

[16]  David B Warheit,et al.  Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[17]  M. Péoc'h,et al.  Dissemination of Wear Particles to the Liver, Spleen, and Abdominal Lymph Nodes of Patients with Hip or Knee Replacement* , 2000, The Journal of bone and joint surgery. American volume.

[18]  R. Cabrini,et al.  An experimental study of the dissemination of Titanium and Zirconium in the body , 2002, Journal of materials science. Materials in medicine.

[19]  R. Cabrini,et al.  Microincineration for the Detection of Titanium in Tissue Sections , 2002 .

[20]  R. Cabrini,et al.  Macrophages Related to Dental Implant Failure , 2003, Implant dentistry.

[21]  L. Boxer,et al.  The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes , 1976 .

[22]  A. Ferguson,et al.  Characteristics of Trace Ions Released from Embedded Metal Implants in the Rabbit , 1962 .

[23]  D. Tasat,et al.  Cytotoxic effect of uranium dioxide on rat alveolar macrophages. , 1987, Environmental research.

[24]  L J Fine,et al.  Abnormalities of pulmonary function and pleural disease among titanium metal production workers. , 1987, Scandinavian journal of work, environment & health.

[25]  I. Gwynn Cell biology at interfaces , 1994 .

[26]  E. Hunziker,et al.  Effect of surface topology on the osseointegration of implant materials in trabecular bone. , 1995, Journal of biomedical materials research.

[27]  Henry Jay Forman,et al.  Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. , 2002, American journal of respiratory and critical care medicine.

[28]  L. Carlsson On the development of a new concept for orthopaedic implant fixation , 1989 .

[29]  H. Hansson,et al.  Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man. , 1981, Acta orthopaedica Scandinavica.

[30]  R. Cabrini,et al.  Titanium transport through the blood stream. An experimental study on rats , 2003, Journal of materials science. Materials in medicine.

[31]  P I Brånemark,et al.  A 15-year study of osseointegrated implants in the treatment of the edentulous jaw. , 1981, International journal of oral surgery.

[32]  P. Morlière,et al.  Impairment of the EGF signaling pathway by the oxidative stress generated with UVA. , 2003, Free radical biology & medicine.

[33]  J Lindström,et al.  Intra-osseous anchorage of dental prostheses. I. Experimental studies. , 1969, Scandinavian journal of plastic and reconstructive surgery.

[34]  Carina B. Johansson,et al.  On tissue reactions to metal implants , 1991 .

[35]  D Buser,et al.  Osseointegration: a reality. , 1998, Periodontology 2000.

[36]  J. Galante,et al.  Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. , 1991, The Journal of bone and joint surgery. American volume.

[37]  F. Afaq,et al.  Cytotoxicity, pro‐oxidant effects and antioxidant depletion in rat lung alveolar macrophages exposed to ultrafine titanium dioxide , 1998, Journal of applied toxicology : JAT.

[38]  S. Toyokuni,et al.  Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds. , 2001, Free radical biology & medicine.

[39]  P. Branemark,et al.  Long-term follow-up study of osseointegrated implants in the treatment of totally edentulous jaws. , 1990, The International journal of oral & maxillofacial implants.

[40]  R. Cabrini,et al.  Effect of dexamethasone on osseointegration: a preliminary experimental study. , 1996, The Journal of oral implantology.

[41]  S. Oikawa,et al.  Distinct mechanisms of oxidative DNA damage induced by carcinogenic nickel subsulfide and nickel oxides. , 2002, Environmental health perspectives.

[42]  K. Donaldson,et al.  Interactions between ultrafine particles and transition metals in vivo and in vitro. , 2002, Toxicology and applied pharmacology.

[43]  J. Brain,et al.  Recovery of free cells from rat lungs by repeated washings. , 1968, Journal of applied physiology.

[44]  W. Phillips,et al.  Activation of the macrophage respiratory burst by phorbol myristate acetate: evidence for both tyrosine-kinase-dependent and -independent pathways. , 1994, Biochimica et biophysica acta.

[45]  L. Boxer,et al.  The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes. , 1976, Blood.

[46]  M. Guglielmotti,et al.  Histomorphometric study of bone healing around laminar implants in experimental diabetes. , 2000, Implant dentistry.