Effect of chronic low-dose microcystin-LR exposure on jejunum apoptosis via RAF/ERK signaling pathway in mouse

Abstract

ABSTRACT Microcystin-LR (MC-LR), a class of cyclic heptapeptide compounds synthesized by cyanobacterial species, presents a significant risk to ecological systems and public health. Exposure to MC-LR was found to induce damage to various organs. One of the target organ systems affected by MC-LR is the gastrointestinal tract (GIT). However, the majority of studies regarding GIT focused on colorectal toxicity, with little attention paid to small intestinal toxic injuries, in particular jejunum. Thus, the aim of this study was to investigate the effects attributed to MC-LR exposure on apoptosis and underlying mechanisms utilizing a mouse jejunum injury model following chronic low-dose MC-LR treatment. A total of 40 C57BL/6 male mice were randomly divided into 4 groups with each group receiving drinking water containing 0, 1, 60, or 120 µg/L MC-LR for a duration of 12 months. Results indicated that exposure to MC-LR induced pathological alterations in jejunal tissue as evidenced by abnormal villous serration, crypt disorganization, and lymphocyte infiltration. TUNEL assays demonstrated a significant increase in apoptotic cell count in the 60 and 120 µg/L groups. The 60 and 120 µg/L MC-LR treatment groups exhibited elevated mRNA expression of Bax accompanied by significant reduction in mRNA expression of Bcl-2. The protein levels of cleaved caspase-3 were markedly elevated in the 60 and 120 µg/L MC-LR groups. The protein expression levels of p-RAF and p-ERK were significantly increased in the 60 and 120 µg/L MC-LR treatment groups. Data demonstrated suggest that the RAF/ERK signaling pathway may be involved in MC-LR- induced jejunal apoptosis.