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The mycotoxin ochratoxin A (OTA) is found widely in agricultural commodities. OTA can induce various toxicities. In this study, rats were gavaged with OTA for different weeks. Then, the expression of microRNAs, mRNAs and proteins were measured in the rat livers treated with OTA for 13 weeks. Our sequencing data suggests that the medial and the high doses of OTA exert different effects on livers. Five distinctive pathways were induced after OTA treatment as collectively demonstrated at miRNA, mRNA and protein levels. Two (primary bile acid biosynthesis and metabolism of xenobiotics by cytochrome P450) are directly associated with liver damage, whereas the remaining pathways (arginine and proline metabolism, cysteine and methionine metabolism and PPAR signaling pathway) cause metabolic disease. This study reveals OTA-induced early hepatotoxicity for the first time by combining multi-omics methods. The novel metabolic pathways may contribute to the pathogenesis of metabolic diseases later in life.

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies