Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non‐human primate animal model

Abstract

An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5 through the use of provocation challenges, and compared V2O5 reactivity before and after subchronic V2O5 exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5-exposed groups (n = 8 each) received equal weekly V2O5 exposures (concentration x time) with different exposure profiles. One V2O5-exposed group received 0.1 mg V2O5 m-3 on Mondays, Wednesday and Fridays, with a twice-weekly peak exposure of 1.1 mg V2O5 m-3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper-reactivity. The other V2O5-exposed group received a constant daily concentration of 0.5 mg V2O5 m-3. A control group (n = 8) received filtered, conditioned air. Pre-exposure challenges with V2O5 produced a concentration-dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5 inhalation did not produce an increase in V2O5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Vanadium pentoxide inhalation

“…[33] In an investigation of cynomolgus monkeys exposed to vanadium pentoxide dust for six hours per day, five days per week for 26 weeks, it demonstrated that airway obstruction accompanied a significant influx of inflammatory cells into alveolar tissue. [34] In an earlier study, it was suggested that vanadium-induced pulmonary inflammatory changes involving polymorphonuclear leukocytes may play an important role in air-flow limitation. [35] Exposure to vanadium may cause a metal fume fever-like syndrome associated with neutrophilic alveolitis associated with marked neutrophilia.…”

Biologic effects of oil fly ash.

“…Inflammatory lung injury after ROFA is accompanied by airway hyperreactivity (35) and an increase in susceptibility to infections (9) in normal animals. The metal composition of the ash appears critical to the development of airway hyperreactivity, as assessed by acetylcholine challenge (9).…”

“…In addition, there are effects of ROFA on sensitization to allergens in animal models of pulmonary allergy, with significant elevations in eosinophils, IL-10, antigen specific immunoglobulin E, and associated immediate bronchoconstriction responses to antigen challenge (36)(37)(38)(39). This effect can be reproduced by the metal leachate of ROFA as well as individual metallic constituents of ROFA (35) and can be abrogated by DMTU pretreatment (40). These results suggest that the oxidative stress presented by metals present in ROFA is responsible for the airway hyperreactivity and sensitization to allergens (41).…”

Toxicity of Vanadium Compounds: Pulmonary and Immune System Targets

“…Subchronic and/or acute exposure of various rodent hosts to V v induced: decreased alveolar macrophage (AM) phagocytosis and lysosomal enzyme activity and release (36,37,38,39); altered lung immune cell population numbers and profiles (40,41,42,43); modified mast cell histamine release (44); increased in situ (but not in vitro) AM expression/production of MIP-2 and KC CXC chemokine mRNA (45); and, airway fibrosis (46,47). This latter study also reported a similar effect when vanadyl sulfate (VOS0 4 ) was used, suggesting that some aspects of the pulmonary immunotoxicity of V may not be valence-dependent.…”