Farnesoid X receptor blockade attenuates morphological damage, intestinal secretion, and prevents mucus loss induced by SARS-CoV-2 spike protein in the mouse intestine

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ID: 319868
2026
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Abstract
Abstract Introduction The SARS-CoV-2 spike protein has been implicated as an important pathogenic factor, including in intestinal disorders. The farnesoid X receptor (FXR), a nuclear receptor highly expressed in the intestine, has been highlighted in several studies investigating its role in different intestinal dysfunctions. Objectives This study evaluated whether FXR blockade attenuates spike-induced morphological alterations and intestinal dysfunction. Methods Balb/c mice were divided into three groups (PBS, Spike, and DY268-antagonist). A 2–3 cm jejunal loop was surgically prepared, and different substances were inoculated into the loops (200 μl of PBS or 200 μl containing 10 μg of spike protein or 100 μl of DY268 at μmol + 100 μl of spike), followed by 4-h resting period before euthanasia. Chloride (Cl−) was measured, and tissue samples were collected for histomorphometry analysis, mucin and MUC2 evaluation, Paneth cell assessment, malondialdehyde (MDA), and glutathione (GSH) levels. Key findings FXR antagonism attenuated alterations in all histomorphometric parameters, maintained mucin expression and Paneth cells and their granules, and reduced MDA levels, while restoring GSH in the intestinal loop. However, further studies are needed to understand the mechanisms by which FXR blockade modulates spike-induced intestinal effects. Conclusions These findings may provide insights into novel targeted strategies for the management of intestinal disorders.
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Authors André Luís Fernandes Lopes, Andreza Ketly da Silva Araújo, Letícia de Sousa Chaves, Esley da Silva Santos, Antonio Carlos Pereira de Oliveira, Katriane Carvalho da Silva, Gabriella Pacheco, Marcelo Biondaro Góis, Lucas Antônio Duarte Nicolau, Jand Venes Rolim Medeiros
Journal The Journal of pharmacy and pharmacology
Year 2026
DOI
10.1093/jpp/rgag074
URL
https://doi.org/10.1093/jpp/rgag074
Keywords Keywords not found

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