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Particles and cellular oxidative and nitrosative stress.

Porter-DW; Leonard-SS; Castranova-V
Particle Toxicology. Donaldson K, Borm P, eds., Boca Raton, FL: CRC Press, 2006 Dec; :119-138
Oxidant stress has been suggested as a causative factor in the initiation and progression of pneumoconiosis (Castranova 2000). Under normal physiological conditions, an equilibrium exists between reactive oxygen species (ROS) and reactive nirotgen species (RNS) generation and antioxidant defenses. However, the inhalation of particles can induce oxidant stress in the lung, disrupting the equilibrium existing between ROS and RNS generation and antioxidant defenses. Specifically, at high particle burdens, the oxidant-antioxidant balance shifts to an excess of oxidant production, causing oxidant injury and initiating the disease process. As reviewed in this chapter, particle exposure can induce oxidant stress by two distinct mechanisms: (1) noncellular particle-mediated ROS generation, and (2) particle-mediated cellular ROS and RNS generation. Non-cellular ROS generation results from, or is enhanced by, Fenton-like reaction(s) involving iron or other transition metals. Particle-mediated cellular ROS and RNS generation results from the stimulation of lung cells, in particular AMs, PMNs, and type II cells. These cells produce ROS via NADPH oxidase, as well as from the mitochondrial electron transport chain. In addition, particle-exposure can induce the expression of the enzyme iNOS, which results in these cells producing nitric oxide, a form of RNS. Both ROS and RNS can induce radical-specific cell damage, such as lipid peroxidation and nitration of tyrosine residues in proteins. Additionally; oxidant stress activates transcription factors (i.e., NF-kappaB and AP-l), which contribute to the transcriptional regulation of genes for inflammatory chemokines and cytokines, as well as growth and fibrogenic factors. Oxidant stress also can induce apoptosis, which at high dust burdens may reach levels which exceed the ability of AMs to clear apoptotic bodies. Free apoptotic bodies may further enhance particle-induced inflammatory and fibrotic processes.
Lung-burden; Lung-disease; Lung-disorders; Lung-function; Oxidative-processes; Oxidative-metabolism; Antioxidants; Respiratory-system-disorders; Pulmonary-system-disorders; Free-radical-generation; Free-radicals
Publication Date
Document Type
Book or book chapter
Donaldson-K; Borm-P
Fiscal Year
NTIS Accession No.
NTIS Price
NIOSH Division
Source Name
Particle Toxicology