15-F2t-isoprostane is not only a specific marker of lipid peroxidation but also demonstrated to have potent bioactivities and can exert deleterious effects via activating
thromboxane A2 receptor (TxA2r). We already demonstrated that lipid peroxidation represents a mechanism of intestinal
ischemia/reperfusion (I/R) injury. But no studies have focused on
15-F2t-isoprostane production and its
biological actions on postischemic intestine during intestinal I/R. This study was carried to investigate whether the mechanism of endogenous
15-F2t-isoprostane action is involved in the pathogenesis of intestinal I/R and administration of synthetic
15-F2t-isoprostane could exacerbate intestinal insult after intestinal I/R in vivo and in vitro. In comparison with that of the
sham control, we reported that endogenous
15-F2t-isoprostane was liberated following intestinal I/R injury in rats, and using the TxA2r antagonist SQ29548 resulted in significant intestinal protection, evidenced by reduced lipid peroxidation,
inflammation, and alleviated intestinal mucosal microvascular vasoconstriction. Further research found that in vivo administration of synthetic
15-F2t-isoprostane exacerbated intestinal I/R injury by disturbing microvascular perfusion and accumulating anaerobic metabolism. Meanwhile,
15-F2t-isoprostane did not change
Hypoxia/Reoxygenation-induced IEC-6 cell viability but aggravated HUVECs cell death in vitro. Collectively, our results showed that locally produced
15-F2t-isoprostane was in proportion to the severity of oxidative stress-induced intestinal injury and its detrimental effects can be attenuated through TxA2r inactivation. Exogenous
15-F2t-isoprostane exacerbated intestinal I/R injury, which may be contributable to its
biological actions on endothelium, rather than intestinal epithelium.