Chronic exposure to low-dose MC-LR induces ileal inflammation in mice through the PI3K/AKT/mTOR pathway.

Abstract

The global phenomenon of cyanobacterial bloom pollution is spreading globally due to climate change and eutrophication. It is well established that harmful cyanobacteria produce a wide range of toxins including microcystin-LR (MC-LR), a cyclic heptapeptide toxin known to damage various organs. The intestinal tract is the main site of MC-LR absorption and one of the targets susceptible to toxicity. Currently, studies on the enterotoxic effects of MC-LR predominantly focused on the colorectum, with limited investigations addressing the impact of microcystins on the small intestine. Therefore, the aim of our study was to examine the impact of chronic 9-month exposure of mice to low-dose 120 μg/L MC-LR in drinking water on ileal inflammation and potential mechanisms underlying these effects. Our findings showed that in mice chronically administered with low-dose MC-LR disorganized intestinal epithelial cells, lymphocytic infiltration and disturbed crypt arrangement were detected. The results of qPCR and Western blot demonstrated that, in comparison to control, the mRNA expression levels of pro-inflammatory factors IL-6, IL-17, IL-18, and IFN-γ were markedly elevated in the ileal tissue of mice treated with MC-LR, associated with significant increases in protein expression levels of p-PI3K, p-AKT, and p-mTOR. Taken together, evidence indicates that MC-LR induces ileal inflammation and histopathological damage involved activation of the PI3K/AKT/mTOR signaling pathway.