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Effects of medium- and long-chain fatty acids on acetaminophen- or rifampicin-induced hepatocellular injury.
Food Science & Nutrition ( IF 3.5 ) Pub Date : 2020-05-19 , DOI: 10.1002/fsn3.1641
Jun Yang 1, 2, 3 , Ting Peng 1, 2, 3 , Jiyong Huang 1, 2, 4 , Guohua Zhang 1, 2, 3 , Jiaheng Xia 1, 2, 4 , Maomao Ma 1, 2, 3 , Danwen Deng 1, 2 , Deming Gong 1, 2, 5 , Zheling Zeng 1, 2, 4
Affiliation  

Drug‐induced liver injury (DILI) is one of the common adverse effects of drug therapy, which is closely associated with oxidative stress, apoptosis, and inflammation response. Medium‐chain fatty acids (MCFA) were reported to relieve inflammation and attenuate oxidative stress. However, little has been known about the hepatoprotective effects of MCFA in DILI. In the present study, acetaminophen (AP) and rifampicin (RFP) were used to establish DILI models in LO2 cells, and the cytoprotective effects of MCFA on hepatocellular injury were investigated. Results showed that the optimal condition for the DILI model was treatment with 10 mM AP or 600 µM RFP for 24 hr. LCFA treatment markedly reduced the cell viability and increased the activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Meanwhile, LCFA treatment aggravated cell apoptosis, mitochondrial dysfunction, and oxidative stress. The mRNA and protein expression levels of inflammatory cytokines (IL‐1β and TNF‐α) were significantly elevated by LCFA. In contrast, MCFA treatment did not significantly affect cell viability, apoptosis, oxidative, stress and inflammation, and it did not produce the detrimental effects on DILI models. Therefore, we proposed that MCFA may be more safe and suitable than LCFA as nutrition support or the selection of daily dietary oil and fat for the patients with DILI.

中文翻译:


中链和长链脂肪酸对对乙酰氨基酚或利福平诱导的肝细胞损伤的影响。



药物性肝损伤(DILI)是药物治疗常见的不良反应之一,与氧化应激、细胞凋亡和炎症反应密切相关。据报道,中链脂肪酸(MCFA)可以缓解炎症并减轻氧化应激。然而,人们对 MCFA 在 DILI 中的保肝作用知之甚少。本研究采用对乙酰氨基酚(AP)和利福平(RFP)在LO2细胞中建立DILI模型,并研究MCFA对肝细胞损伤的细胞保护作用。结果显示,DILI 模型的最佳条件是用 10 mM AP 或 600 µM RFP 处理 24 小时。 LCFA处理显着降低了细胞活力并增加了丙氨酸转氨酶、天冬氨酸转氨酶和乳酸脱氢酶的活性。同时,LCFA治疗加剧了细胞凋亡、线粒体功能障碍和氧化应激。 LCFA 显着升高炎症细胞因子(IL-1β 和 TNF-α)的 mRNA 和蛋白表达水平。相比之下,MCFA治疗不会显着影响细胞活力、细胞凋亡、氧化、应激和炎症,并且不会对DILI模型产生有害影响。因此,我们提出MCFA可能比LCFA更安全、更适合作为DILI患者的营养支持或日常膳食油脂的选择。
更新日期:2020-05-19
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