Dietary zearalenone alters gill epithelial morphology and subsequent risk of infection: Insights from a freshwater grass carp (Ctenopharyngodon idella) model

Abstract

The mechanical action of zearalenone (ZEA) on different species has been the focus of attention. However, current knowledge of the mode of action and detailed mechanism of ZEA in aquatic species remains limited. According to the maximum detectable dose of commercial fish feed (511 μg kg−1), 1440 freshwater edible grass carp (Ctenopharyngodon idella) with an initial weight of 15.34 ± 0.06 g that were fed six graded levels of dietary ZEA (0, 535, 1041, 1548, 2002 and 2507 μg kg−1 diet). After 70 d, impaired gill epithelial barrier function was confirmed in ZEA-exposed grass carp in terms of the differential expression of tight junctions (TJs), increased oxidative stress levels, and excessive apoptosis promoted cell death. Subsequently, the health status of the fish was determined by immersion (3 h) of Flavobacterium columnare. ZEA-exposed fish displayed the highest incidence of gill rot at 3 d postinfection. Concordantly, at higher doses, ZEA could significantly decrease immune component [(e.g., acid phosphatase (ACP), lysozyme (LZ) and Complement 3 (C3)] activities and antimicrobial peptides (AMPs) transcription abundance and increase substantially inflammatory cytokines. Furthermore, we found that the nuclear factor-erythroid 2-related factor 2 (Nrf2), the nuclear factor κB (NF-κB), and the target of rapamycin (TOR) may be partially involved in associated regulation, thus indicating a potential regulatory network affected by ZEA. In summary, our findings suggest that ZEA disrupts the barrier function of fish gills and increases the risks of pathogen infection. The current recommended guidance values for ZEA in aquaculture (2000 μg kg−1) are insufficient to preclude toxic potential, and increased public concern about ZEA in feed and feedstuff is essential.