The multiple biotoxicity integrated study in grass carp (Ctenopharyngodon idella) caused by Ochratoxin A: Oxidative damage, apoptosis and immunosuppression

Ochratoxin A (OTA) is a common hazardous food contaminant that seriously endangers human and animal health. However, limited study is focused on aquatic animal. This research investigated the multiple biotoxicity of OTA on spleen (SP) and head kidney (HK) in grass carp and its related mechanism. Our data showed that, dietary supplemented with OTA above 1209 μg/kg caused histopathological damages by decreasing the number of lymphocytes and necrotizing renal parenchymal cells. Meanwhile, OTA caused oxidative damage and reduced the isoforms mRNAs transcripts of antioxidant enzymes (e.g., GPX1, GPX4, GSTO) partly due to suppressing NF-E2-related factor 2 (Nrf2). OTA triggered apoptosis through mitochondria and death receptor pathway potentially by p38 mitogen-activated protein kinase (p38MAPK) activation. Besides, OTA exacerbated inflammation by down-regulation of anti-inflammatory factor (e.g., IL-10, IL-4) and up-regulations of pro-inflammatory factors (e.g., TNF-α, IL-6), which could be ascribed to signaling meditation of Janus kinase / signal transducer and activator of transcription (JAK/STAT). Additionally, the safe upper limits of OTA were estimated to be 677.6 and 695.08 μg/kg based on the immune-related indexes (C3 contents in the SP and LZ activities in the HK, respectively). Our study has provided a wide insight for toxicological assessment of feed pollutant in aquatic animals.