# Effects of High Concentrations of Flumequine on CYP Gene Expression and Histopathology in Olive Flounder, Paralichthys olivaceus

## TL;DR

This study shows that high doses of flumequine increase CYP gene activity and cause liver and organ damage in olive flounder.

## Contribution

The study reveals novel insights into the toxicity and gene expression effects of high flumequine concentrations in olive flounder.

## Key findings

- High flumequine concentrations (4×) significantly increased CYP gene expression, especially CYP2B4 (46.6-fold).
- Histopathological changes like hepatic atrophy and lymphocytic infiltration were observed at high flumequine doses.
- Toxic effects were more severe at 4× flumequine compared to 1× concentration in liver, spleen, and kidneys.

## Abstract

Olive flounder is a valuable aquaculture species in South Korea, and a variety of antibiotics are used to treat bacterial diseases in aquatic organisms. In our study, we examined the effect of the quinolone-class flumequine on olive flounder. The results of the drug metabolism genes and histopathological symptoms indicate increased gene expression levels and a severe lesions tendency at the high concentration of flumequine (4×) compared to the low concentration (1×). This study may contribute to understanding the effects of flumequine on drug metabolism and general toxicity.

Flumequine is an antibiotic that is used to treat bacterial diseases in aquaculture. Fish express drug-metabolizing genes in response to antibiotic exposure. However, studies on the effects of high flumequine concentrations on drug metabolism genes and histopathology of the olive flounder are limited. To investigate the response of olive flounder to flumequine, we administered it at different concentrations. We analyzed the expression of drug metabolism genes (CYP) in the liver and histopathological lesions in the liver, spleen, and kidneys. The gene expression levels of CYP were higher at the highest flumequine concentration tested (4×) than at the lowest flumequine concentration (1×). The highest CYP gene expression level was observed for CYP2B4 (46.6-fold) at 4× flumequine compared to that in the control group. Hepatic atrophy, lymphocytic infiltration, and hematopoiesis were observed in the liver, spleen, and kidney at 4× flumequine between 3 and 24 h compared to 1× flumequine, respectively. These results contribute to a better understanding of drug metabolism and the general toxicity of pharmaceutical exposure in olive flounder.