Pulmonary toxicity following acute coexposures to diesel particulate matter and α-quartz crystalline silica in the Sprague-Dawley rat

Abstract

The effects of acute pulmonary coexposures to silica and diesel particulate matter (DPM), which may occur in various mining operations, were investigated in vivo. Rats were exposed by intratracheal instillation (IT) to silica (50 or 233 µg), DPM (7.89 or 50 µg) or silica and DPM combined in phosphate-buffered saline (PBS) or to PBS alone (control). At one day, one week, one month, two months and three months postexposure bronchoalveolar lavage and histopathology were performed to assess lung injury, inflammation and immune response. While higher doses of silica caused inflammation and injury at all time points, DPM exposure alone did not. DPM (50 µg) combined with silica (233 µg) increased inflammation at one week and one-month postexposure and caused an increase in the incidence of fibrosis at one month compared with exposure to silica alone. To assess susceptibility to lung infection following coexposure, rats were exposed by IT to 233 µg silica, 50 µg DPM, a combination of the two or PBS control one week before intratracheal inoculation with 5 × 10 Listeria monocytogenes. At 1, 3, 5, 7 and 14 days following infection, pulmonary immune response and bacterial clearance from the lung were evaluated. Coexposure to DPM and silica did not alter bacterial clearance from the lung compared to control. Although DPM and silica coexposure did not alter pulmonary susceptibility to infection in this model, the study showed that noninflammatory doses of DPM had the capacity to increase silica-induced lung injury, inflammation and onset/incidence of fibrosis.

Crystalline silica particles cause rapid NLRP3-dependent mitochondrial depolarization and DNA damage in airway epithelial cells

“…The alveolar surface area in mice is 82 cm 2 [ 39 ], and assuming a distribution to alveoli an inhaled dose of 25 μg will give a dose of 0.3 μg/cm 2 in this compartment. In rats a single inhaled dose of 233 μg, but not 50 μg, provoked increased levels of IL-18 within a week [ 40 ]. A lung burden of 200 μg/rat causes persistent inflammation in sub-chronic exposure studies and the NOEL for inflammation has been estimated to be 0.3–0.7 μg/cm 2 [ 16 ].…”

The pro-inflammatory effects of combined exposure to diesel exhaust particles and mineral particles in human bronchial epithelial cells

“…Few other studies have assessed the effects of combined exposure to minerals and combustion particles in experimental systems [ 64 – 66 ]. Tomašek et al [ 66 ] exposed an alveolar 3D co-culture at air–liquid interface (ALI) and pseudo-ALI to volcanic ash particles in combination with the National Institute of Standards and Technology (NIST) standard reference material (SRM) 2975, a DEP derived from an industrial forklift.…”

“…Similar results were reported in the same cell model exposed to volcanic ash and complete gasoline exhaust, which produced no significant change in cytotoxicity or markers of oxidative stress and inflammation [ 65 ]. In a study by Farris et al [ 64 ], the effects of SRM 2975 and quartz were assessed in rats after intratracheal instillation of doses relevant to workers in hydraulic fracturing operations. While combined exposure modified the effects on lung injury and inflammation, no consistent increase in biological endpoints were detected across doses and time points, and DEP tended to decrease the quartz-induced levels of several inflammatory markers in the lung when administered together [ 64 ].…”

“…In a study by Farris et al [ 64 ], the effects of SRM 2975 and quartz were assessed in rats after intratracheal instillation of doses relevant to workers in hydraulic fracturing operations. While combined exposure modified the effects on lung injury and inflammation, no consistent increase in biological endpoints were detected across doses and time points, and DEP tended to decrease the quartz-induced levels of several inflammatory markers in the lung when administered together [ 64 ]. Nevertheless, combined exposure induced an increase in the number of neutrophils, which persisted up to 1 month after exposure, indicating increased lung inflammation.…”

Inhale, exhale: Why particulate matter exposure in animal models are so acute? Data and facts behind the history

“… [58] Intratracheal instillation To assess susceptibility to lung infection following coexposure to particulate matter. [59] Intratracheal instillation In this study, we evaluated the primary oxidative stress produced in the lung by crystalline silica (SiO 2 ) in the early phase after SiO 2 exposure. The aim of this study is to understand the crystalline SiO 2 -induced pulmonary oxidative stress in the early phase.…”