Abstract
Context
The addition of silver (Ag) to food items, and its migration from food packaging and appliances results in a dietary exposure in humans, estimated to 70–90 µg Ag/day. In view of the well-known bactericidal activity of Ag ions, concerns arise about a possible impact of dietary Ag on the gut microbiota (GM), which is a master determinant of human health and diseases. Repeated oral administration of Ag acetate (AgAc) can also cause systemic toxicity in rats with reported NOAELs of 4 mg AgAc/b.w./d for impaired fertility and 0.4 mg AgAc/b.w./d for developmental toxicity.
Objective
The objective of this study was to investigate whether oral exposure to AgAc can induce GM alterations at doses causing reproductive toxicity in rats.
Methods
Male and female Wistar rats were exposed during 10 weeks to AgAc incorporated into food (0, 0.4, 4 or 40 mg/kg b.w./d), and we analyzed the composition of the GM (α- and β-diversity). We documented bacterial function by measuring short-chain fatty acid (SCFA) production in cecal content. Ferroxidase activity, a biomarker of systemic Ag toxicity, was measured in serum.
Results and conclusions
From 4 mg/kg b.w./d onwards, we recorded systemic toxicity, as indicated by the reduction of serum ferroxidase activity, as well as serum Cu and Se concentrations. This systemic toxic response to AgAc might contribute to explain reprotoxic manifestations. We observed a dose-dependent modification of the GM composition in male rats exposed to AgAc. No impact of AgAc exposure on the production of bacterial SCFA was recorded. The limited GM changes recorded in this study do not appear related to a reprotoxicity outcome.
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Data availability
Data and material are available from the authors upon reasonable request.
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This work was supported financially by the European Precious Metals Federation (EPMF, Brussels, Belgium).
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The Louvain centre for Toxicology and Applied Pharmacology (LTAP) is accredited to conduct animal experiments (reference LA12312, Bruxelles Environnement). The experimental design and procedures for this work were approved by the local ethical committee for biomedical research at UCLouvain (reference 2018/UCL/MD/012).
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Lison, D., Ambroise, J., Leinardi, R. et al. Systemic effects and impact on the gut microbiota upon subacute oral exposure to silver acetate in rats. Arch Toxicol 95, 1251–1266 (2021). https://doi.org/10.1007/s00204-021-02998-1
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DOI: https://doi.org/10.1007/s00204-021-02998-1