Crosstalk of oxidative damage, apoptosis, and autophagy under endoplasmic reticulum (ER) stress involved in thifluzamide-induced liver damage in zebrafish (Danio rerio)

Crosstalk of oxidative damage, apoptosis, and autophagy under endoplasmic reticulum (ER) stress involved in thifluzamide-induced liver damage in zebrafish (Danio rerio)

2018

Although the hepatotoxicity of thifluzamide in zebrafish has been characterized, its toxic mechanisms have not been fully explored. The present study demonstrated that thifluzamide damaged the zebrafish liver and endoplasmic reticulum (ER). In addition, thifluzamide significantly changed the expression of genes encoding antioxidant proteins and increased the malondialdehyde (MDA) content, leading to oxidative damage in zebrafish liver. Additionally, the autophagic ultrastructure was observed by transmission electron microscopy (TEM), and LC3-I/LC3-II conversion was obviously upregulated under western blotting (WB) measurements, verifying that autophagy was induced by thifluzamide. Moreover, the activities of Caspase-3 and Caspase-9 were obviously decreased, indicating that apoptosis was inhibited in adult zebrafish exposed to a higher concentration of thifluzamide. In summary, oxidative damage and autophagy but not apoptosis under ER injury might lead to the hepatotoxicity of thifluzamide in zebrafish. Our findings provide a new mechanistic insight into the toxicity of thifluzamide in zebrafish.

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