title: Toxicity of titanium dioxide nanoparticles: Effect of dose and time on biochemical disturbance, oxidative stress and genotoxicity in mice.
abstract: The toxic impact of titanium dioxide nanoparticles (TiO2NPs) on human health is of prime importance owing to their wide uses in many commercial industries. In the present study, the effect of different doses and exposure time durations of TiO2NPs (21nm) inducing oxidative stress, biochemical disturbance, histological alteration and cytogenetic aberration in mice liver and bone marrow was investigated. Different doses of (TiO2NPs) (50, 250 and 500mg/kg body weight) were each daily intrapertioneally injected to mice for 7, 14 and 45days. Aspartate and alanine aminotransferases (AST &ALT), gamma glutamyl transpeptidase (GGT), total protein, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) levels were measured. The work was extended to evaluate the liver histopathological pattern and the chromosomal aberration in mice spinal cord bone marrow. The results revealed severe TiO2NPs toxicity in a dose and time dependent manner with positive correlation (r=0.98) for most investigated biochemical parameters. The same observation was noticed for the histological analysis. In case of cytogenetic study, chromosomal aberrations were demonstrated after injection of TiO2NPs with 500mg/kg b. wt. for 45days. In conclusion, the selected biochemical parameters and the liver architectures were influenced with dose and time of TiO2NPs toxicity, while the genetic disturbance started at the high dose of exposure and for long duration. Further studies are needed to fulfil the effect of TiO2NPs on pharmaceutical and nutritional applications.
authors.affiliation: Therapeutic Chemistry Departments, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, Egypt.
authors.forename: Maha Z
authors.initials: MZ
authors.lastname: Rizk
authors.affiliation: Therapeutic Chemistry Departments, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, Egypt.
authors.forename: Sanaa A
authors.initials: SA
authors.lastname: Ali
authors.affiliation: Therapeutic Chemistry Departments, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, Egypt. Electronic address: manal_hamed@yahoo.com.
authors.forename: Manal A
authors.initials: MA
authors.lastname: Hamed
authors.affiliation: Therapeutic Chemistry Departments, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, Egypt.
authors.forename: Nagy Saba
authors.initials: NS
authors.lastname: El-Rigal
authors.affiliation: Therapeutic Chemistry Departments, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, Egypt.
authors.forename: Hanan F
authors.initials: HF
authors.lastname: Aly
authors.affiliation: Genetics and Cytology Departments, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, Egypt.
authors.forename: Heba H
authors.initials: HH
authors.lastname: Salah
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002869:Chromosome Aberrations / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053768:Metal Nanoparticles / Q000009:adverse effects*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D014025:Titanium / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; C009495:titanium dioxide; D008315:Malondialdehyde; D014025:Titanium; D002374:Catalase; D000410:Alanine Transaminase; D005978:Glutathione
keywords: Liver function; Liver histology; Microsomal aberration; Oxidative stress; Titanium dioxide nanoparticles