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姬松茸多糖减轻荷 Lewis 瘤小鼠氟尿嘧啶的毒性。

Reduction of 5-fluorouracil-induced toxicity by Sarcodon aspratus polysaccharides in Lewis tumor-bearing mice.

机构信息

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China.

School of Life Sciences, Anhui University, Hefei 230601, Anhui, China; Anhui Key Laboratory of Modern Biomanufacturing, Hefei 230601, Anhui, China; Anhui Key Laboratory of Eco-engineering and Biotechnology, Hefei 230601, Anhui, China.

出版信息

Int J Biol Macromol. 2020 Nov 15;163:232-239. doi: 10.1016/j.ijbiomac.2020.05.004. Epub 2020 Jun 17.

Abstract

5-Fluorouracil (5-Fu) is an effective anticarcinogenic agent, however, continuous use of 5-Fu may cause severe side effects. The goal of this study was to investigate the effectiveness of Sarcodon aspratus polysaccharides (SATP) in alleviating 5-Fu-induced toxicity in Lewis tumor-bearing mice. Lewis tumor-bearing mice were treated with saline, SATP, 5-Fu or 5-Fu + SATP. The results indicated that compared to the 5-Fu group, the 5-Fu + SATP group showed effective amelioration of the liver, kidney and small intestine injury caused by 5-Fu and decreases in the levels of related biochemical indicators, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea nitrogen (BUN). Additionally, the combination therapy enhanced the quality of life and immune organ indexes of mice. Further mechanistic studies indicated that the 5-Fu + SATP group showed a decrease in hepatotoxicity caused by 5-Fu via a reduction in the levels of interleukin-1β (IL-1β), an increase in the expression of Bcl-2 and decreases in the expression of p-p38, p-JNK and Bax. Collectively, the results indicated that SATP could significantly alleviate the toxicity of 5-Fu in Lewis tumor-bearing mice and showed the hepatoprotective capability of SATP via its effect on the expression levels of inflammatory factors and components of the MAPK/P38/JNK pathway, which shows that it may be a potential adjuvant for the chemotherapeutic drug 5-Fu in cancer treatment.

摘要

氟尿嘧啶(5-Fu)是一种有效的抗癌药物,然而,连续使用 5-Fu 可能会引起严重的副作用。本研究的目的是探讨云芝多糖(SATP)对减轻 Lewis 荷瘤小鼠 5-Fu 毒性的作用。Lewis 荷瘤小鼠分别用生理盐水、SATP、5-Fu 或 5-Fu+SATP 处理。结果表明,与 5-Fu 组相比,5-Fu+SATP 组能有效改善 5-Fu 引起的肝、肾和小肠损伤,并降低相关生化指标如天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和尿素氮(BUN)的水平。此外,联合治疗还提高了小鼠的生活质量和免疫器官指数。进一步的机制研究表明,5-Fu+SATP 组通过降低白细胞介素-1β(IL-1β)水平,增加 Bcl-2 表达,降低 p-p38、p-JNK 和 Bax 表达,减轻 5-Fu 引起的肝毒性。综上所述,SATP 能显著减轻 Lewis 荷瘤小鼠 5-Fu 的毒性,并通过影响炎症因子和 MAPK/P38/JNK 通路组成部分的表达水平发挥其肝保护作用,表明它可能是癌症治疗中 5-Fu 化疗药物的一种潜在佐剂。

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