Chronic exposure to microcystin-LR reduces thyroid hormone levels by activating p38/MAPK and MEK/ERK signal pathway

Microcystin-LR (MC-LR) is the most toxic and abundant microcystin that produced by cyanobacteria. Previous studies have shown MC-LR had acute toxic to thyroid, however, the mechanism is still unclear, and the effect of long-term, low-dose MC-LR on thyroid remains uncertain. In this study, we investigated the chronic, low-dose effect of MC-LR on mouse thyroid tissues and thyroid hormone metabolism. MC-LR was orally administered to mice at 0, 1, 10, 20 and 40 μg/L for 6 consecutive months for histopathological and immunoblot analysis. Nthy-ori 3-1 cells were cultured in various concentrations of MC-LR (0, 0.5, 5, 50, 500 nmol/L) for indicated time, meanwhile the cell viability and proteins change were tested. From our study, the chronic, low-dose MC-LR exposure can disturb thyroid hormone synthesis and metabolism through activating the p38/MAPK and MEK/ERK signaling pathways, then up-regulating the expression of type 3 deiodinase. These data support the potential toxic effects of MC-LR on thyroid tissue and thyroid hormone metabolism.