The prophylactic use of polyvinylpyridine-N-oxide (PVNO) in baboons exposed to quartz dust

Goldstein, B.; Rendall, R.E.G.

doi:10.1016/s0013-9351(87)80214-1

Cited by 12 publications

(9 citation statements)

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“…Most likely due to limited i n vivo coating stability and/or a reduced availability of already lung-resident quartz particles for curative post-exposure coating, neither PVPNO nor aluminium salts brought a real breakthrough in quartz passivation from the preventive and more importantly curative point of view (Weller, 1975; Zhao et al , 1983; Prügger et al , 1984; Goldstein and Rendall, 1987; Bégin et al , 1993; Dufresne et al , 1994; Bégin et al , 1995), raising the need for more promising preventive quartz-coating strategies for industries with potentially hazardous quartz exposure. In contrast to AL and PVPNO, exhibiting mechanisms based on ionic forces and hydrogen bonding, respectively (Fubini, 1998a, 1998b; Albrecht, et al , 2007), organosilane compounds, with their hydrolysed products organosilanols and organosiloxanes, are able to react covalently with quartz surface silanol groups (Wiessner et al , 1990), envisaging potentially more stable quartz coatings.…”

Section: Discussionmentioning

confidence: 99%

“…Polyvinylpyridine- N -oxide (PVPNO) and aluminium salts have already been tested as non-covalent surface modifications to treat or prevent silicosis, however, with limited success (Weller, 1975; Zhao et al , 1983; Prügger et al , 1984; Bégin et al , 1986; Goldstein and Rendall, 1987; Dubois et al , 1988; Dufresne et al , 1994; Bégin et al , 1995). PVPNO forms strong hydrogen bonds via NO − groups, thus masking negatively charged SiO − groups (reviewed by Castranova, 1995), whereas aluminium lactate (AL) can block surface charges and radical formation via the aluminium cation and related ionic forces (Bégin et al , 1986; Brown et al , 1989; Duffin et al , 2001; Albrecht et al , 2004, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Organosilane-Based Coating of Quartz Species from the Traditional Ceramics Industry: Evidence of Hazard Reduction Using In Vitro and In Vivo Tests

Ziemann

Escrig

Bonvicini

et al. 2017

Annals of Work Exposures and Health

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The exposure to respirable crystalline silica (RCS), e.g. quartz, in industrial settings can induce silicosis and may cause tumours in chronic periods. Consequently, RCS in the form of quartz and cristobalite has been classified as human lung carcinogen category 1 by the International Agency for Research on Cancer in 1997, acknowledging differences in hazardous potential depending on source as well as chemical, thermal, and mechanical history. The physico-chemical determinants of quartz toxicity are well understood and are linked to density and abundance of surface silanol groups/radicals. Hence, poly-2-vinylpyridine-N-oxide and aluminium lactate, which effectively block highly reactive silanol groups at the quartz surface, have formerly been introduced as therapeutic approaches in the occupational field. In the traditional ceramics industry, quartz-containing raw materials are indispensable for the manufacturing process, and workers are potentially at risk of developing quartz-related lung diseases. Therefore, in the present study, two organosilanes, i.e. Dynasylan® PTMO and Dynasylan® SIVO 160, were tested as preventive, covalent quartz-coating agents to render ceramics production safer without loss in product quality. Coating effectiveness and coating stability (up to 1 week) in artificial alveolar and lysosomal fluids were first analysed in vitro, using the industrially relevant quartz Q1 as RCS model, quartz DQ12 as a positive control, primary rat alveolar macrophages as cellular model system (75 µg cm−2; 4 h of incubation ± aluminium lactate to verify quartz-related effects), and lactate dehydrogenase release and DNA strand break induction (alkaline comet assay) as biological endpoints. In vitro results with coated quartz were confirmed in a 90-day intratracheal instillation study in rats with inflammatory parameters as most relevant readouts. The results of the present study indicate that in particular Dynasylan® SIVO 160 (0.2% w/w of quartz) was able to effectively and stably block toxicity of biologically active quartz species without interfering with technical process quality of certain ceramic products. In conclusion, covalent organosilane coatings of quartz might represent a promising strategy to increase workers’ safety in the traditional ceramics industry.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Organosilane-Based Coating of Quartz Species from the Traditional Ceramics Industry: Evidence of Hazard Reduction Using In Vitro and In Vivo Tests

Ziemann

Escrig

Bonvicini

et al. 2017

Annals of Work Exposures and Health

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“…The polymer PVNO has been investigated for its potential prophylactic and therapeutic use in silica and silica-containing dust induced fibrosis, albeit with limited success [ 37 - 39 ]. Next to addition, adsorption of PVNO onto the crystalline silica surface has been shown to blunt its reactivity via a mechanism that is considered to involve H-bonding of its NO groups with the reactive silanol groups at the quartz surface.…”

Section: Discussionmentioning

confidence: 99%

Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs

et al. 2014

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RationaleMineral particles in the lung cause inflammation and silicosis. In myeloid and bronchial epithelial cells the inflammasome plays a role in responses to crystalline silica. Thioredoxin (TRX) and its inhibitory protein TRX-interacting protein link oxidative stress with inflammasome activation. We investigated inflammasome activation by crystalline silica polymorphs and modulation by TRX in vitro, as well as its localization and the importance of silica surface reactivity in rats.MethodsWe exposed bronchial epithelial cells and differentiated macrophages to silica polymorphs quartz and cristobalite and measured caspase-1 activity as well as the release of IL-1β, bFGF and HMGB1; including after TRX overexpression or treatment with recombinant TRX. Rats were intratracheally instilled with vehicle control, Dörentruper quartz (DQ12) or DQ12 coated with polyvinylpyridine N-oxide. At days 3, 7, 28, 90, 180 and 360 five animals per treatment group were sacrificed. Hallmarks of silicosis were assessed with Haematoxylin-eosin and Sirius Red stainings. Caspase-1 activity in the bronchoalveolar lavage and caspase-1 and IL-1β localization in lung tissue were determined using Western blot and immunohistochemistry (IHC).ResultsSilica polymorphs triggered secretion of IL-1β, bFGF and HMGB1 in a surface reactivity dependent manner. Inflammasome readouts linked with caspase-1 enzymatic activity were attenuated by TRX overexpression or treatment. At day 3 and 7 increased caspase-1 activity was detected in BALF of the DQ12 group and increased levels of caspase-1 and IL-1β were observed with IHC in the DQ12 group compared to controls. DQ12 exposure revealed silicotic nodules at 180 and 360 days. Particle surface modification markedly attenuated the grade of inflammation and lymphocyte influx and attenuated the level of inflammasome activation, indicating that the development of silicosis and inflammasome activation is determined by crystalline silica surface reactivity.ConclusionOur novel data indicate the pivotal role of surface reactivity of crystalline silica to activate the inflammasome in cultures of both epithelial cells and macrophages. Inhibitory capacity of the antioxidant TRX to inflammasome activation was evidenced. DQ12 quartz exposure induced acute and chronic functional activation of the inflammasome in the heterogeneous cell populations of the lung in associated with its crystalline surface reactivity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0058-0) contains supplementary material, which is available to authorized users.

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“…When considering quartz-induced DNA damage and its possible role in carcinogenicity it should be emphasized that surface reactivity is one of the key factors contributing to the pathogenicity associated with quartz inhalation (7,18,19). For instance, in the past decades various in vivo studies demonstrated that quartz-induced silicosis could be inhibited by the administration of compounds such as aluminium salts and polyvinylpyridine-N-oxide (PVNO), which are known to modify the surface reactivity of the quartz particles (20)(21)(22)(23)(24). In general, the reactivity of the particle surface is closely related to the ability of quartz to generate ROS (19,25,26).…”

Section: Introductionmentioning

confidence: 99%

DNA damage in lung epithelial cells isolated from rats exposed to quartz: role of surface reactivity and neutrophilic inflammation

Knaapen

Albrecht²,

Becker³

et al. 2002

Carcinogenesis

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Respirable quartz has been classified as a human lung carcinogen (IARC, 1997). However, the mechanisms involved in quartz-induced carcinogenesis remain unclear. The aim of the present study was to investigate acute DNA damage in epithelial lung cells from rats exposed to quartz. Since surface reactivity is considered to play a crucial role in the toxicity of quartz, the effect of surface modifying agents polyvinylpyridine-N-oxide (PVNO) and aluminium lactate (AL) was evaluated. Therefore, rats were instilled with quartz (DQ12, 2 mg/rat) or quartz treated with PVNO or AL. After 3 days animals were killed and brochoalveolar lavage (BAL) was performed to evaluate inflammatory cell influx. BAL-fluid levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP) and total protein were used as lung damage markers. Neutrophil activation was assessed by myeloperoxidase (MPO) measurement, and total antioxidant capacity of the BAL-fluid was determined using the TEAC (trolox equivalent antioxidant capacity) assay. Lung epithelial cells were isolated and DNA strand breakage was determined by single cell gel electrophoresis (comet assay). DNA damage was significantly increased in epithelial cells from rats instilled with DQ12, whereas no enhanced DNA strand breakage was observed when quartz was treated with PVNO or AL. Total protein, LDH and TEAC were increased in rats treated with native quartz, and this was inhibited by both coatings. A significant correlation between neutrophil numbers and MPO levels was observed, indicating neutrophil activation. Inhibition of DNA damage by both coatings was paralleled by a reduction of neutrophil influx as well as MPO activity. In this study we provide evidence that modification of the particle surface prevents DNA strand breakage in epithelial lung cells from quartz-exposed rats. Furthermore, the present data show the feasibility of our in vivo model to evaluate the role of inflammation, antioxidant status, and cytotoxicity in particle-induced DNA damage.

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The prophylactic use of polyvinylpyridine-N-oxide (PVNO) in baboons exposed to quartz dust

Cited by 12 publications

References 7 publications

Organosilane-Based Coating of Quartz Species from the Traditional Ceramics Industry: Evidence of Hazard Reduction Using In Vitro and In Vivo Tests

Organosilane-Based Coating of Quartz Species from the Traditional Ceramics Industry: Evidence of Hazard Reduction Using In Vitro and In Vivo Tests

Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs

DNA damage in lung epithelial cells isolated from rats exposed to quartz: role of surface reactivity and neutrophilic inflammation

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