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短期接触环丙沙星和微塑料会导致肝内胆汁淤积,而长期接触会降低能量代谢并增加肥胖风险。

Short-term exposure to ciprofloxacin and microplastic leads to intrahepatic cholestasis, while long-term exposure decreases energy metabolism and increases the risk of obesity.

作者信息

Hou Lirui, Fu Yuhan, Zhao Chong, Fan Lihong, Hu Hongbo, Yin Shutao

机构信息

Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, 17 Qinghua East Road, Haidian District, Beijing 100083, China.

College of Veterinary Medicine, China Agricultural University, Yunamingyuan West Road, Haidian District, Beijing 100193, China.

出版信息

Environ Int. 2025 May;199:109511. doi: 10.1016/j.envint.2025.109511. Epub 2025 May 3.

DOI:10.1016/j.envint.2025.109511
PMID:40328087
Abstract

Microplastics (MPs) and antibiotics are pervasive pollutants that may pose a risk to human health. Studies have shown that both MPs and antibiotics adversely affect lipid metabolism and increase the risk of obesity. However, it remains unclear whether combined exposure to these pollutants intensify the cumulative detrimental effect on obesity and metabolism. This study demonstrated the impact of exposure to polystyrene MPs (PS, 25 nm) and ciprofloxacin (CIP), both individually and combined, for 30 d and 90 d on the hepatic metabolism of male C57BL/6J mice. The results showed that mice exposed to PS and CIP for either 30 d or 90 d exhibited lipid metabolism disorders such as increased body weight, enlarged adipocytes, triglyceride accumulation in the liver, and higher HDL-C. Differentially expressed hepatic proteins were identified via proteomic analysis. The findings indicated that exposure for 30 d caused abnormal bile acid (BA) secretion in the liver and inhibited the BA secretion pathway, which resulted in intrahepatic cholestasis. Furthermore, exposure for 90 d resolved cholestasis and reduced the overall number of differentially expressed proteins. Intestinal pathology revealed more severe damage after exposure for 30 d, while 90 d exposure decreased the adverse effect. Combined CIP and PS exposure caused damage to the organism. However, the adaptive capacity of the organism during prolonged exposure mitigated the damage caused by both, but did not imply the complete eradication of adverse effects. This study found that 90 d exposure to PS and CIP resulted in weight gain, possibly due to changes in the gut flora and suppressed energy metabolism. These results indicated that simultaneous exposure to CIP and PS exacerbated the adverse impact on the liver, causing short-term intrahepatic cholestasis. Prolonged exposure reduced the energy metabolism in the body, exhibiting varied toxicity outcomes and mechanisms at different exposure durations. This study offers novel insights into the effect of MPs and antibiotic CIP exposure on metabolic abnormalities and provides a scientific basis for assessing these risks. It also emphasizes that the adverse effect resulting from 30 d (short-term) toxic exposure may not persist and that long-term chronic toxicity needs warrants.

摘要

微塑料(MPs)和抗生素是普遍存在的污染物,可能对人类健康构成风险。研究表明,微塑料和抗生素都会对脂质代谢产生不利影响,并增加肥胖风险。然而,尚不清楚同时接触这些污染物是否会加剧对肥胖和代谢的累积有害影响。本研究证明了单独及联合暴露于聚苯乙烯微塑料(PS,25纳米)和环丙沙星(CIP)30天和90天对雄性C57BL/6J小鼠肝脏代谢的影响。结果表明,暴露于PS和CIP 30天或90天的小鼠表现出脂质代谢紊乱,如体重增加、脂肪细胞增大、肝脏中甘油三酯积累以及高密度脂蛋白胆固醇(HDL-C)升高。通过蛋白质组学分析鉴定了肝脏中差异表达的蛋白质。研究结果表明,暴露30天会导致肝脏胆汁酸(BA)分泌异常,并抑制BA分泌途径,从而导致肝内胆汁淤积。此外,暴露90天可缓解胆汁淤积并减少差异表达蛋白质的总数。肠道病理学显示,暴露30天后损伤更严重,而暴露90天则可降低不良反应。CIP和PS联合暴露会对生物体造成损害。然而,长期暴露期间生物体的适应能力减轻了两者造成的损害,但并不意味着完全消除了不利影响。本研究发现,暴露于PS和CIP 90天会导致体重增加,这可能是由于肠道菌群的变化和能量代谢受抑制所致。这些结果表明,同时暴露于CIP和PS会加剧对肝脏的不利影响,导致短期肝内胆汁淤积。长期暴露会降低体内能量代谢,在不同暴露持续时间表现出不同的毒性结果和机制。本研究为微塑料和抗生素CIP暴露对代谢异常的影响提供了新的见解,并为评估这些风险提供了科学依据。它还强调,30天(短期)毒性暴露产生的不利影响可能不会持续存在,长期慢性毒性需要引起重视。

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