Gao Peng, Chang Cheng, Liang Jieling, Du Fen, Zhang Ruilin
TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China.
Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
Int J Mol Sci. 2024 Feb 27;25(5):2744. doi: 10.3390/ijms25052744.
Amoxicillin is commonly used in clinical settings to target bacterial infection and is frequently prescribed during pregnancy. Investigations into its developmental toxicity and effects on disease susceptibility are not comprehensive. Our present study examined the effects of embryonic amoxicillin exposure on liver development and function, especially the effects on susceptibility to non-alcoholic fatty liver disease (NAFLD) using zebrafish as an animal model. We discovered that embryonic amoxicillin exposure did not compromise liver development, nor did it induce liver toxicity. However, co-treatment of amoxicillin and clavulanic acid diminished BESP expression, caused bile stasis and induced liver toxicity. Embryonic amoxicillin exposure resulted in elevated expression of lipid synthesis genes and exacerbated hepatic steatosis in a fructose-induced NAFLD model, indicating embryonic amoxicillin exposure increased susceptibility to NAFLD in zebrafish larvae. In summary, this research broadens our understanding of the risks of amoxicillin usage during pregnancy and provides evidence for the impact of embryonic amoxicillin exposure on disease susceptibility in offspring.
阿莫西林在临床环境中常用于治疗细菌感染,孕期也经常会开具此药。对其发育毒性及对疾病易感性影响的研究并不全面。我们目前的研究以斑马鱼为动物模型,考察了胚胎期暴露于阿莫西林对肝脏发育和功能的影响,尤其是对非酒精性脂肪性肝病(NAFLD)易感性的影响。我们发现,胚胎期暴露于阿莫西林并未损害肝脏发育,也未诱发肝毒性。然而,阿莫西林与克拉维酸联合使用会降低BESP表达,导致胆汁淤积并诱发肝毒性。在果糖诱导的NAFLD模型中,胚胎期暴露于阿莫西林会导致脂质合成基因表达升高,并加剧肝脂肪变性,这表明胚胎期暴露于阿莫西林会增加斑马鱼幼体对NAFLD的易感性。总之,本研究拓宽了我们对孕期使用阿莫西林风险的认识,并为胚胎期暴露于阿莫西林对后代疾病易感性的影响提供了证据。