title: Lipoxygenase pathway mediates increases of airway resistance and lung inflation induced by exposure to nanotitanium dioxide in rats.
abstract: Nanotitanium dioxide particle (nTiO2) inhalation has been reported to induce lung parenchymal injury. After inhalation of nTiO2, we monitored changes in 5-lipoxygenase, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) mRNA in rat lung tissue. Lung function parameters include specific airway resistance (SRaw), peak expiratory flow rate (PEF), functional residual capacity (FRC), and lung compliance (Cchord); blood white blood cell count (WBC), nitric oxide (NO), hydrogen peroxide, and lactic dehydrogenase (LDH); and lung lavage leukotriene C4, interleukin 6 (IL6), tumor necrotic factor α (TNFα), hydroxyl radicals, and NO. Leukotriene receptor antagonist MK571 and 5-lipoxygenase inhibitor MK886 were used for pharmacologic intervention. Compared to control, nTiO2 exposure induced near 5-fold increase in 5-lipoxygenase mRNA expression in lung tissue. iNOS mRNA increased while eNOS mRNA decreased. Lavage leukotriene C4; IL6; TNFα; NO; hydroxyl radicals; and blood WBC, NO, hydrogen peroxide, and LDH levels rose. Obstructive ventilatory insufficiency was observed. MK571 and MK886 both attenuated the systemic inflammation and lung function changes. We conclude that inhaled nTiO2 induces systemic inflammation, cytokine release, and oxidative and nitrosative stress in the lung. The lipoxygenase pathway products, mediated by oxygen radicals and WBC, play a critical role in the obstructive ventilatory insufficiency induced by nTiO2.
authors.affiliation: Department of Nursing, St. Mary's Medicine Nursing and Management College, Yilan County 266, Taiwan.
authors.forename: Jyu-Feng
authors.initials: JF
authors.lastname: Lee
authors.affiliation: Department of Emergency and Critical Care, Cheng-Hsin General Hospital, Taipei 112, Taiwan.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Tung
authors.affiliation: Department of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan ; Division of Chest Medicine, Department of Internal Medicine, Shin Kong Wu-Ho-Su Memorial Hospital, Taipei 11101, Taiwan.
authors.forename: Diana Yuwung
authors.initials: DY
authors.lastname: Yeh
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Chi-Mei Foundation Medical Center, Tainan 71004, Taiwan.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fong
authors.affiliation: Department of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Young
authors.affiliation: Department of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan ; Department of Pathology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan.
authors.forename: Fur-Jiang
authors.initials: FJ
authors.lastname: Leu
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D005652:Functional Residual Capacity; D007700:Kinetics; D007958:Leukocyte Count; D017997:Leukotriene C4 / Q000378:metabolism; D058945:Lipoxygenases / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000336:Aerosols; D012333:RNA, Messenger; C009495:titanium dioxide; D017997:Leukotriene C4; D009569:Nitric Oxide; D014025:Titanium; D058945:Lipoxygenases; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen