Adverse effects of triclosan on kidney in mice: Implication of lipid metabolism disorders.
Adverse effects of triclosan on kidney in mice: Implication of lipid metabolism disorders.
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DOI：
10.1016/j.jes.2021.11.032
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发表时间：
2023
影响因子：
6.9
通讯作者：
Wei Huang;Guodong Cao;Chengliang Deng;Yanyan Chen;Tao Wang;Dahan Chen;Z. Cai
中科院分区：
文献类型：
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作者：
Wei Huang;Guodong Cao;Chengliang Deng;Yanyan Chen;Tao Wang;Dahan Chen;Z. Cai
三氯生（TCS）是一种普遍存在于日常消费品中的抗菌剂。已有研究表明TCS可引起肝毒性、内分泌干扰、免疫功能紊乱和甲状腺功能损害。肾脏在排除毒素方面至关重要，而TCS对肾脏的影响尚未得到充分表征。本研究的目的是研究TCS暴露对小鼠肾功能的影响及其可能的机制。雄性C57 BL/6小鼠经口给予TCS 10和100 mg/（kg·d），连续13周。将TCS溶解于二甲基亚砜（DMSO）中，并用玉米油稀释以进行暴露。含有DMSO的玉米油用作溶剂对照。收集血清和肾组织用于研究。评估了与肾功能、氧化应激、炎症和纤维化相关的生物标志物。结果表明，TCS可引起肾损伤，表现为血清肌酐、尿素氮和尿酸等肾功能指标升高，氧化应激、促炎细胞因子和纤维化指标升高，且呈剂量依赖性，100 mg/（kg·d）组更为明显。与脂质代谢相关的代谢产物的质谱分析表明，在100 mg/（kg·d）TCS暴露的小鼠肾脏中发生脂质蓄积和脂肪酸氧化缺陷。这些过程可能导致脂肪毒性和能量消耗，从而导致肾纤维化和功能下降。综上所述，本研究表明，TCS可诱导小鼠肾脏脂质蓄积和脂肪酸代谢紊乱，这可能有助于肾功能损害。本研究进一步拓宽了我们对TCS不良影响的认识。
Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.