posted on 2020-03-17, 16:05authored byHolger Sieg, Benjamin-Christoph Krause, Claudia Kästner, Linda Böhmert, Dajana Lichtenstein, Jutta Tentschert, Harald Jungnickel, Peter Laux, Albert Braeuning, Valerie Fessard, Andreas F. Thünemann, Andreas Luch, Alfonso Lampen
Aluminum
(Al) can be taken up from food, packaging, or the environment
and thus reaches the human gastrointestinal tract. Its toxic potential
after oral uptake is still discussed. The fate of different solid
and ionic Al species during the passage through the digestive tract
is the focus of this research, as well as the cellular effects caused
by these different Al species. The present study combines the physicochemical
processing of three recently studied Al species (metallic Al0, mineral Al2O3, and soluble AlCl3) in artificial digestion fluids with in vitro cell
systems for the human intestinal barrier. Inductively coupled plasma
mass spectrometry (ICP-MS) and small-angle X-ray scattering (SAXS)
methods were used to characterize the Al species in the artificial
digestion fluids and in cell culture medium for proliferating and
differentiated intestinal Caco-2 cells. Cytotoxicity testing and cellular
impedance measurements were applied to address the effects of digested
Al species on cell viability and cell proliferation. Microarray-based
transcriptome analyses and quantitative real-time PCR were conducted
to obtain a deeper insight into cellular mechanisms of action and
generated indications for cellular oxidative stress and an influence
on xenobiotic metabolism, connected with alterations in associated
signaling pathways. These cellular responses, which were predominantly
caused by formerly ionic Al species and only at very high concentrations,
were not impacted by artificial digestion. A two-directional conversion
of Al between ionic species and solid particles occurred throughout
all segments of the gastrointestinal tract, as evidenced by the presence
of nanoscaled particles. Nevertheless, this presence did not increase
the toxicity of the respective Al species.