Biocompatibility and inflammatory response of silver tungstate, silver molybdate, and silver vanadate microcrystals

Abstract

Silver tungstate (α-Ag₂WO₄), silver molybdate (β-Ag₂MoO₄), and silver vanadate (α-AgVO₃) microcrystals have shown interesting antimicrobial properties. However, their biocompatibility is not yet fully understood. Cytotoxicity and the inflammatory response of silver-containing microcrystals were analyzed in THP-1 and THP-1 differentiated as macrophage-like cells, with the alamarBlue™ assay, flow cytometry, confocal microscopy, and ELISA. The present investigation also evaluated redox signaling and the production of cytokines (TNFα, IL-1β, IL-6, and IL-8) and matrix metalloproteinases (MMP-8 and -9). The results showed that α-AgVO₃ (3.9 μg/mL) did not affect cell viability (p > 0.05). α-Ag₂WO₄ (7.81 μg/mL), β-Ag₂MoO₄ (15.62 μg/mL), and α-AgVO₃ (15.62 μg/mL) slightly decreased cell viability (p ≤ 0.003). All silver-containing microcrystals induced the production of O₂ ^- and this effect was mitigated by Reactive Oxygen Species (ROS) scavenger and N-acetylcysteine (NAC). TNFα, IL-6 and IL-1β were not detected in THP-1 cells, while their production was either lower (p ≤ 0.0321) or similar to the control group (p ≥ 0.1048) for macrophage-like cells. The production of IL-8 by both cellular phenotypes was similar to the control group (p ≥ 0.3570). The release of MMP-8 was not detected in any condition in THP-1 cells. Although MMP-9 was released by THP-1 cells exposed to α-AgVO₃ (3.9 μg/mL), no significant difference was found with control (p = 0.7). Regarding macrophage-like cells, the release of MMP-8 and -9 decreased in the presence of all microcrystals (p ≤ 0.010). Overall, the present work shows a promising biocompatibility profile of, α-Ag₂WO₄, β-Ag₂MoO₄, and α-AgVO₃ microcrystals.

Keywords: cytokines; macrophages; matrix metalloproteinases, reactive oxygen species; monocytes; silver-based metal oxides.