Nitric oxide and reactive oxygen species production causes progressive damage in rats after cessation of silica inhalation.

Our laboratory has previously reported results from a rat silica inhalation study which determined that, even after silica exposure ended, pulmonary inflammation and damage progressed with subsequent fibrosis development. In the present study, the relationship between silica exposure, nitric oxide (NO) and reactive oxygen species (ROS) production, and the resultant pulmonary damage is investigated in this model. Rats were exposed to silica (15 mg/m3, 6 h/day) for either 20, 40, or 60 days.

Progression of lung inflammation and damage in rats after cessation of silica inhalation.

Human epidemiologic studies have found that silicosis may develop or progress even after occupational exposure has ended, suggesting that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure. We previously described the time course of rat pulmonary responses to silica inhalation as biphasic, the initial phase characterized by increased but controlled pulmonary inflammation and damage. However, after a threshold lung burden was exceeded, rapid progression of silica-induced pulmonary disease occurred.

Effect of inhaled crystalline silica in a rat model: time course of pulmonary reactions.

Numerous investigations have been conducted to elucidate mechanisms involved in the initiation and progression of silicosis. However, most of these studies involved bolus exposure of rats to silica, i.e.

Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica.

In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-kappa B activation, cytotoxic damage, and fibrosis were detailed. In this study, we investigated the temporal relationship between silica inhalation, nitric oxide (NO), and reactive oxygen species (ROS) production, and damage mediated by these radicals in the rat. Rats were exposed to a silica aerosol (15 mg/m(3) silica, 6 h/day, 5 days/wk) for 116 days.

Time course of pulmonary response of rats to inhalation of crystalline silica: NF-kappa B activation, inflammation, cytokine production, and damage.

In vitro studies suggest that silica-induced lung disease may be linked to processes regulated by nuclear factor-kappa B (NF-kappa B) activation, but this has not been examined in vivo. Rats were exposed to a silica aerosol of 15 mg/m(3) (6 h/day, 5 days/wk) for 116 days, and bronchoalveolar lavage (BAL) was conducted at various times during the exposure. Silica-induced pulmonary inflammation and damage were determined by measuring BAL cell differentials and first BAL fluid lactate dehydrogenase (LDH) activity and serum albumin concentrations, respectively.

Time course of pulmonary response of rats to inhalation of crystalline silica: histological results and biochemical indices of damage, lipidosis, and fibrosis.

Previous studies have determined that alpha-quartz (crystalline silica) can cause pulmonary inflammation, damage, and fibrosis. However, the temporal relationship between silica inhalation and pulmonary inflammation, damage, and fibrosis has not been fully examined. To address this gap in our knowledge of silica-induced pulmonary fibrosis, a chronic inhalation study using rats was designed.

Augmentation of pulmonary reactions to quartz inhalation by trace amounts of iron-containing particles.

Fracturing quartz produces silica-based radicals on the fracture planes and generates hydroxyl radicals (.OH) in aqueous media. .

Monitoring of aromatic amine exposures in workers at a chemical plant with a known bladder cancer excess.

Background: In April 1991, an excess of bladder cancer cases among workers employed at a chemical manufacturing facility in Niagara Falls, NY, was reported. This excess was primarily confined to 708 workers who had ever been employed in the rubber chemicals manufacturing area of the plant, where the aromatic amines aniline and o-toluidine have historically been used.

Purpose: An environmental and biological monitoring survey was conducted to evaluate current exposures to aniline and o-toluidine in the rubber chemicals department.

Particle activity and in vivo pulmonary response to freshly milled and aged alpha-quartz.

This study examined the possibility of freshly fractured alpha-quartz being more toxic and inflammatory in vivo than aged quartz of the same composition and particle size. Fresh quartz was generated by a jet mill, and used immediately, while aged dust was stored for two months before use. Both the production of hydrogen peroxide and hydroxyl radicals and the analysis of surface radicals verified the enhanced surface activity of fresh quartz.

Biological monitoring for occupational exposures to o-toluidine and aniline.

Epidemiological evidence that occupational exposure to o-toluidine and aniline is associated with an increased risk of bladder cancer led to efforts to identify biomarkers of workplace exposures to these aromatic amines. For the determination of o-toluidine and aniline in worker urine specimens, a method using high performance liquid chromatography (HPLC) followed by electrochemical detection was developed. The limits of detection were 0.