Caffeic acid phenethyl ester ameliorates colistin-induced nephrotoxicity in rats via modulation of FOXO1/Nrf2/Sirt1 axis

IF 2.9 4区医学 Q2 Medicine Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-10-24 DOI:10.1111/1440-1681.70000

Mohammed Z. Nasrullah, Thikryat Neamtalllah, Mohannad Alshibani, Alaa A. Bagalagel, Ahmad O. Noor, Hussain T. Bakhsh, Ashraf B. Abdel-Naim

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Abstract

Background

Colistin (Cst) is one of the antimicrobial peptides and is reserved for use against multi-drug-resistant Gram-negative bacteria. However, the clinical value of Cst is limited by its nephrotoxic adverse effects. Caffeic acid phenethyl ester (CAPE) is a honeybee propolis flavonoid recognised for its diverse pharmacological potential. It has demonstrated d antioxidant and anti-inflammatory properties, as well as protective effects against chemically induced toxicity in variuos biological systems. This study aimed to investigate the impact of CAPE on nephrotoxicity induced in rats by Cst.

Methods

Animals were randomly divided into five groups. Group 1 served as control, group 2 received CAPE (10 mg/kg) orally, group 3 received Cst IP, group 4 received Cst + CAPE (5 mg/kg) and group 5 received Cst + CAPE (10 mg/kg). All treatments were given daily for 10 consecutive days.

Results

CAPE notably attenuated Cst-inducednephrotoxicity as shown by reducing urea serum levels, creatinine, cystatin C, urinary protein contents and urinary N-acetyl-β-D-glucosaminidase (NAG). This was confirmed by histological investigations that indicated amelioration of histopathological changes in the kidney architecture as well as the deposition of collagen in renal tissues. CAPE exhibited antioxidant effects supported by the prevention of rise in Cst-induced lipid peroxidation and depletion of superoxide dismutase and catalase enzymatic activities. In addition, CAPE inhibited the expression of the inflammatory markers including tumour necrosis factor-α, nuclear factor kappa B and interleukin-6. These actions were associated with modulation of messenger ribonucleic acid (mRNA) expression of Bax and Bcl-2 in favour of anti-apoptosis. CAPE inhibited Cst-induced rise in forkhead box O1 (FOXO1) expression and downregulation of nuclear factor erythroid 2–related factor 2 (Nrf2) and Sirtuin 1 (Sirt1) immune-expression.

Conclusion

CAPE protects against nephrotoxicity induced by Cst in ratsprimarily through its antioxidant, antiinflammatory and antiapoptotic activities. These pritective effects are mediated via modulation of FOXO1/Nrf2/Sirt1 axis.

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咖啡酸苯乙酯通过调节 FOXO1/Nrf2/Sirt1 轴改善可乐定诱导的大鼠肾毒性

背景：可乐定（Cst）是抗菌肽之一，专门用于抗耐多种药物的革兰氏阴性菌。然而，Cst 的临床价值因其肾毒性不良反应而受到限制。咖啡酸苯乙酯（CAPE）是一种蜜蜂蜂胶类黄酮，具有多种药理潜力。它具有抗氧化和抗炎特性，在各种生物系统中对化学诱导的毒性具有保护作用。本研究旨在探讨 CAPE 对 Cst 诱导的大鼠肾毒性的影响：动物随机分为五组。第 1 组为对照组，第 2 组口服 CAPE（10 毫克/千克），第 3 组 IP 服用 Cst，第 4 组服用 Cst + CAPE（5 毫克/千克），第 5 组服用 Cst + CAPE（10 毫克/千克）。所有治疗每天进行，连续 10 天：结果：通过降低尿素血清水平、肌酐、胱抑素 C、尿蛋白含量和尿液中的 N-乙酰-β-D-氨基葡萄糖苷酶（NAG），CAPE 显著减轻了 Cst 引起的肾毒性。组织学调查也证实了这一点，调查显示肾脏结构的组织病理学变化以及肾组织中胶原蛋白的沉积均有所改善。CAPE 具有抗氧化作用，可防止 Cst 诱导的脂质过氧化反应的增加以及超氧化物歧化酶和过氧化氢酶酶活性的消耗。此外，CAPE 还能抑制炎症标志物的表达，包括肿瘤坏死因子-α、核因子卡巴 B 和白细胞介素-6。这些作用与 Bax 和 Bcl-2 信使核糖核酸（mRNA）表达的调节有关，有利于抗凋亡。CAPE抑制了Cst诱导的叉头框O1（FOXO1）表达的上升以及核因子红细胞2相关因子2（Nrf2）和Sirtuin 1（Sirt1）免疫表达的下调：结论：CAPE 主要通过其抗氧化、抗炎和抗细胞凋亡活性来保护大鼠免受 Cst 引起的肾毒性。这些保护作用是通过调节 FOXO1/Nrf2/Sirt1 轴介导的。

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来源期刊

Clinical and Experimental Pharmacology and Physiology 医学-生理学

CiteScore

6.20

自引率

0.00%

发文量

128

审稿时长

6 months

期刊介绍： Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.