γ-射线合成的 5-氟尿嘧啶纳米凝胶与 5-氟尿嘧啶大鼠模型的肝毒性比较。

Wael Em Barakat, Fatma Sm Moawed, Esraa Sa Ahmed, Omayma Ar Abo-Zaid
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引用次数: 0

摘要

简介5-氟尿嘧啶(5-FU)是一种常规化疗药物,在临床上的使用会对肝脏产生有害影响。因此,有必要寻找一种危害较小的替代药物,以尽量减少对肝脏的损害。本研究旨在观察 5-氟尿嘧啶纳米凝胶如何影响 5-FU 诱导的大鼠肝损伤:为了诱导肝损伤,雄性白化大鼠腹腔注射 5-FU(12.5 毫克/千克),每周三次,连续注射一个月。组织病理学检查和血清丙氨酸和天门冬氨酸氨基转移酶(ALT 和 AST)活性测定用于评估肝损伤的严重程度,此外还测定了肝氧化应激和抗氧化标记物。此外,还检测了血红素加氧酶-1(HO-1)、核因子红细胞2相关因子2(Nrf2)及其抑制剂Kelch样ECH相关蛋白-1(Keap-1)的肝脏基因表达,以及肿瘤坏死因子-α(TNF-α)和白细胞介素(IL-1β、IL-6)等肝脏炎症介质:结果:5-Fu 纳米凝胶除了抑制肝脏炎症介质(TNF- α、IL-1β 和 IL-6)外,还改善了肝脏结构和功能(ALT 和 AST),从而有效减轻了 5-FU 引起的肝损伤。此外,5-FU 纳米凝胶还通过维持细胞稳态 Keap-1/Nrf2/HO-1 通路,缓解了受损的氧化还原状态,恢复了抗氧化系统:因此,与 5-FU 相比,5-Fu 纳米凝胶的肝脏毒性更低,这可能是由于它缓解了肝脏炎症并调节了细胞氧化还原途径。
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The hepatotoxicity of γ-radiation synthesized 5-fluorouracil nanogel versus 5-fluorouracil in rats model.

Introduction: The clinical use of 5-fluorouracil (5-FU), a routinely used chemotherapy medication, has a deleterious impact on the liver. Therefore, it is necessary to find a less harmful alternative to minimize liver damage. This study was designed to see how 5-fluorouracil nanogel influenced 5-FU-induced liver damage in rats.

Methods: To induce liver damage, male albino rats were injected intraperitoneally with 5-FU (12.5 mg/kg) three doses/week for 1 month. The histopathological examination together with measuring the activities of serum alanine and aspartate aminotransferase enzymes (ALT and AST) were used to evaluate the severity of liver damage besides, hepatic oxidative stress and antioxidant markers were also measured. The hepatic gene expression of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α) and interleukins (IL-1β, IL-6) were detected.

Results: 5-Fu nanogel effectively attenuated 5-FU-induced liver injury by improving the hepatic structure and function (ALT and AST) besides the suppression of the hepatic inflammatory mediators (TNF- α, IL-1β and IL-6). Additionally, 5-FU nanogel alleviated the impaired redox status and restored the antioxidant system via maintaining the cellular homeostasis Keap-1/Nrf2/HO-1 pathway.

Conclusion: Consequently, 5-Fu nanogel exhibited lower liver toxicity compared to 5-FU, likely due to the alleviation of hepatic inflammation and the regulation of the cellular redox pathway.

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来源期刊
International Journal of Immunopathology and Pharmacology
International Journal of Immunopathology and Pharmacology Immunology and Microbiology-Immunology
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发文量
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期刊介绍: International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
期刊最新文献
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