Transcriptomic Association Analysis of the Metabolic Mechanism of Sulfamethoxazole in Channel Catfish (Ictalurus punctatus)

Simple Summary Sulfamethoxazole is a commonly used antimicrobial drug in aquaculture. In order to understand its effect on the liver transcriptome of channel catfish, we orally administered a certain proportion of sulfamethoxazole into the fish and analyzed the changes in the transcriptome to determine the effect of the drug on the fish. By studying changes in the transcriptome, we found that the drug acted on drug metabolizing functions in the liver. Stimulated fish try to ensure the normal expression of their physiological functions by accelerating the operation of various metabolisms. The detoxification process is facilitated by promoting glucuronidation in the fish liver; while lipid metabolism is increased, the antioxidant pathway is affected, and the glucose xenobiotic pathway is enhanced in order to maintain energy homeostasis and to ensure a normal energy supply for metabolism. Other cellular metabolisms are also carried out to repair damaged normal organisms. This study provides a reference for understanding drug metabolism in channel catfish and provides a warning about the use of the drug. Abstract Sulfamethoxazole is a widely used antimicrobial drug used to treat bacterial diseases in aquaculture. To understand the gene expression in channel catfish liver after treatment with sulfamethoxazole, in this study, the treatment group received sulfamethoxazole (100 mg/kg bw), which was administered orally once, and samples were taken at 5 h, 12 h, and 6 d after the administration of sulfamethoxazole, while the control group was orally administered sterile water. To further identify potentially significant genes, a transcriptome analysis using RNA-seq was carried out. More than 50 million high-quality reads were found. After filtering and quality analysis, these reads were identified as 54,169,682, 51,313,865, 51,608,845, and 49,333,491. After counting 23,707 of these transcripts for gene expression, it was discovered that 14,732 of them had genes with differential expression. Moreover, we found that the annotation with the most GO variation was "cellular process" (1616 genes), "metabolic process" (1268 genes), "binding" (1889 genes), and "catalytic activity" (1129 genes). KEGG pathways showed that the "metabolic pathway" was the pathway that was significantly enriched in both experimental groups when comparing the experimental groups: 5 h and 12 h (128 genes); 5 h and 6 d (332 genes); and 12 h and 6 d (348 genes). Also, UDP- glucuronosyltransferase (ugt), which is associated with glucuronidation, and UDP-glucuronosyltransferase 2C1-like (ugt2a1) showed significant upregulation. Carboxylesterase 5A-like (ces3), which promotes fatty acyl and cholesteryl ester metabolism, and the glutathione transferase family were upregulated in the expression of sulfamethoxazole metabolism in the liver, which significantly affected the metabolic effects of the drug. Meanwhile, dypd, uck2b, and rrm2, which are related to nucleotide synthesis and metabolism, were upregulated. Our study extends the knowledge of gene expression in drug metabolism in channel catfish and further provides insight into the molecular mechanism of sulfamethoxazole metabolism.