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: Jyu-Feng Lee, Shu-Ping Tung, David Wang, Diana Yuwung Yeh, Yao Fong, Yu-Chung Young, Fur-Jiang Leu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2014 Pg. 485604 ( 2014) ISSN: 1942-0994 [Electronic] United States
• PMID: 24693335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aerosols
• RNA, Messenger
• titanium dioxide
• Leukotriene C4
• Nitric Oxide
• Titanium
• Lipoxygenases
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Oxygen

Topics

• Administration, Inhalation
• Aerosols (administration & dosage)
• Airway Resistance (drug effects)
• Animals
• Bronchoalveolar Lavage Fluid
• Functional Residual Capacity
• Kinetics
• Leukocyte Count
• Leukotriene C4 (metabolism)
• Lipoxygenases (genetics, metabolism)
• Lung (drug effects, enzymology, pathology, physiopathology)
• Male
• Nanoparticles (administration & dosage, toxicity)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Nitric Oxide Synthase Type III (genetics, metabolism)
• Oxygen (metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Titanium (administration & dosage, toxicity)