Althagafy Hanan S, Hassanein Emad H M
Department of Biochemistry, Faculty of Science, University of Jeddah, Saudi Arabia.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
Int Immunopharmacol. 2025 Feb 20;148:114092. doi: 10.1016/j.intimp.2025.114092. Epub 2025 Jan 17.
5-Fluorouracil (5-FU) is a DNA analog used in chemotherapy to treat various tumors. However, the clinical use of 5-FU is limited due to its severe adverse effects, particularly its nephrotoxicity. Morin (MRN) is a flavanol found in many different plants, including those in the Moraceae family, and has anti-inflammatory and antioxidant bioactivities. The protective effects of MRN against experimental 5-FU-induced kidney injury were investigated in this work. The rats were assigned to four groups in our study: control, MRN (50 mg/kg), 5-FU (30 mg/kg), and 5-FU + MRN. The administration of MRN caused a significant (P < 0.05) decrease in the serum urea and creatinine levels and a reduction in the histopathological changes induced by 5-FU, as shown by H&E, PAS, and Sirius red staining. IHC shows that MRN attenuates renal oxidative stress induced by 5-FU via co-activation of Nrf2, HO-1, and FXR. MRN protects against renal inflammation induced by 5-FU, as evidenced by decreased TNF-α and IL-6 levels in the rat kidney mediated by the downregulation of the ERK1/2 and VCAM-1 proteins and decreased NF-κB phosphorylation as shown by Western blotting. These findings support using MRN as a novel and promising treatment for 5-FU-induced nephrotoxicity.
5-氟尿嘧啶（5-FU）是一种用于化疗治疗各种肿瘤的DNA类似物。然而，由于其严重的不良反应，特别是肾毒性，5-FU的临床应用受到限制。桑色素（MRN）是一种存在于许多不同植物中的黄烷醇，包括桑科植物，具有抗炎和抗氧化生物活性。本研究探讨了MRN对实验性5-FU诱导的肾损伤的保护作用。在我们的研究中，将大鼠分为四组：对照组、MRN（50mg/kg）、5-FU（30mg/kg）和5-FU+MRN。如苏木精-伊红（H&E）、过碘酸-雪夫（PAS）和天狼星红染色所示，给予MRN可使血清尿素和肌酐水平显著降低（P<0.05），并减少5-FU诱导的组织病理学变化。免疫组化（IHC）显示，MRN通过共同激活核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）和法尼酯X受体（FXR）减轻5-FU诱导的肾氧化应激。MRN可保护大鼠肾脏免受5-FU诱导的炎症，如通过下调细胞外信号调节激酶1/2（ERK1/2）和血管细胞黏附分子-1（VCAM-1）蛋白介导的大鼠肾脏中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平降低以及蛋白质印迹法显示的核因子κB（NF-κB）磷酸化降低所证明。这些发现支持将MRN作为一种新型且有前景的治疗5-FU诱导的肾毒性的方法。
