主催: 日本毒性学会
会議名: 第50回日本毒性学会学術年会
開催日: 2023/06/19 - 2023/06/21
Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesic and antipyretic drugs. In order to investigate the toxicity of APAP, we used zebrafish embryos or larvae as model animals to test the effect of APAP on zebrafish embryos or larvae. Zebrafish embryos were exposed to 0 (control), 0.01, 0.1, 1, and 5 mM APAP from 4 hour post fertilization (hpf) to detection. Morphological changes in zebrafish were observed every 24 hpf, and behavioral changes were detected from 18 to 120 hpf. Histological changes, transcriptional analysis, and expression changes of thyroid-related genes were performed at 72 hpf. Experimental data showed that APAP caused pericardial edema in zebrafish embryos or larvae (42.7%, P<0.05), and pigmentation decreased (66.6%, P<0.05). Behavioral analyzes showed that APAP (0.1-5 mM) exposure also resulted in a significant increase in coiling behavior in early-developing embryos (18-32 hpf). However, when tested at 120 hpf, APAP (0.1 and 1 mM) increased the swimming distance of zebrafish larvae, while 5 mM APAP decreased the swimming distance of zebrafish larvae (100%, P<0.05). KEGG discovery of retinol metabolism, Fanconi anemia pathway, and tyrosine metabolism. Differentially expressed lncRNAs were identified to affect pigment development (fabp4b, cyp7a1, rpe65a) as well as pigment production in the thyroid (tyrp1b, fabp4b). RT-PCR assay also showed that APAP treatment led to a decrease in zebrafish thyroid peroxidase (tpo) and thyroid hormone receptor β (thrβ) mRNA expression (P < 0.05). The deleterious effects of APAP on zebrafish embryos may be due to its disruptive effect on the functional regulation of the thyroid hormone (THs) system. It is suggested should use APAP with caution.