Effects of Elevated Oxytetracycline on Cytochrome P450 and Immune-Related Gene Expression and Histopathological Alterations in Olive Flounder, Paralichthys olivaceus

Oxytetracycline (OTC) is widely used in aquaculture to treat bacterial diseases, but its effects on drug metabolism and immune responses remain poorly understood in olive flounder (Paralichthys olivaceus). This study investigated the effects of OTC immersion for 1 h at different concentrations on the expression profile of drug metabolism- and immune-related genes and the histopathological changes in the gills and liver of olive flounder. The expression of Paralichthys olivaceus cytochrome P450 (PoCYP), Paralichthys olivaceus diphosphate (UDP)-glucuronosyltransferases (PoUGTs), and immune-related genes significantly increased at 12 and 24 h and then decreased at 72 h in the 100 and 200 ppm groups. By contrast, the 400 ppm group exhibited variable expression patterns depending on the gene and tissue. The highest expression levels were observed for PoIL-1β in the gills (22.7-fold) and PoCYP27B1 in the liver (58.0-fold) in the 400 ppm group. Histopathological analysis revealed macrophage activation in the liver at 72 h in the 200 ppm group, whereas epithelial edema and mild aneurysmal changes in the gills and macrophage activation in the liver were observed in the 400 ppm group. These findings provide insights into the effects of OTC exposure on drug metabolism and immune responses in olive flounder.