Aluminum (Al) is the most abundant and ubiquitous metal in the environment. The main route of human exposure to Al is through food and water intake. Although human exposure to Al is common, the influence of Al on the gastrointestinal tract remains poorly understood.
We aimed to further understand the toxic effect of Al and to elucidate the underlying cellular mechanisms in the intestinal barrier.
The human intestinal epithelial cell line HT-29 and C57BL6 mice were exposed to
at
(
) and
body weight (13 weeks), respectively. In cell culture experiments, intracellular oxidative stress, inflammatory protein and gene expression, and intestinal epithelial permeability were measured. In animal studies, histological examination, gene expression, and myeloperoxidase (MPO) activity assays were conducted.
Cellular oxidative stress level (superoxide production) in
-treated cells (
,
) was approximately 38-fold higher than that of the control. Both protein and mRNA expression of tight junction (TJ) components (occludin and claudin-1) in
-treated cells (
,
) was significantly lower than that of the control. Transepithelial electrical resistance (TEER) decreased up to 67% in
-treated cells (
,
) compared with that of the control, which decreased approximately 7%. Al activated extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B (
), resulting in mRNA expression of matrix metalloproteinase-9, myosin light-chain kinase, and inflammatory cytokines [tumor necrosis factor alpha (
),
(
), and IL-6] in HT-29 cells. Moreover, oral administration of
to mice induced pathological alteration, MPO activation, and inflammatory cytokine (
,
, and IL-6) production in the colon.
Al induced epithelial barrier dysfunction and inflammation via generation of oxidative stress, down-regulation of the TJ proteins, and production of inflammatory cytokines in HT-29 cells. In addition, Al induced toxicity in the colon by increasing the levels of inflammatory cytokines and MPO activity and induced histological damage in a mouse model. Our data suggest that Al may be a potential risk factor for human intestinal diseases. https://doi.org/10.1289/EHP5701....

Effects of Aluminum on the Integrity of the Intestinal Epithelium: An in Vitro and in Vivo Study

10.1289/EHP5701