Nonsteroidal anti-inflammatory
drugs (NSAIDs) like indomethacin
and others are widely used in clinics, but they have the potential
to cause severe gastrointestinal damage including intestinal barrier
dysfunction. Thus, two flavonols galangin and kaempferol with or without
heat treatment (100 °C, 30 min) were assessed for their effect
on indomethacin-damaged rat intestine epithelial (IEC-6) cells. In
total, the cell exposure of 300 μmol/L indomethacin for 24 h
caused cell toxicity efficiently, resulting in decreased cell viability,
enhanced lactate dehydrogenase (LDH) release or reactive oxygen species
(ROS) production, and obvious barrier loss. Meanwhile, pretreatment
of the cells with these flavonols for 24 and 48 h before the indomethacin
exposure could alleviate cytotoxicity and especially barrier loss,
resulting in increased cell viability and transepithelial resistance,
decreased LDH release, ROS production, and paracellular permeability,
together with the promoted expression of three tight junction proteins
zonula occluden-1, occludin, and claudin-1. Moreover, the intracellular
Ca
2+
concentration and expression levels of p-JNK and p-Src
arisen from the indomethacin damage were also reduced by the flavonols,
suggesting an inhibited calcium-mediated JNK/Src activation. Consistently,
galangin showed higher activity than kaempferol to the cells, while
the heated flavonols were less efficient than the unheated counterparts.
It is thus highlighted that the two flavonols could alleviate indomethacin
cytotoxicity and combat against the indomethacin-induced barrier loss
in IEC-6 cells, but heat treatment of the flavonols would weaken the
two beneficial functions.
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