Syringetin ameliorates thallium sulphate induced renal dysfunction via regulating Nrf2/Keap-1, TLR4/HMGB1/RAGE and NF-κB pathway

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-06-02 DOI:10.1016/j.tice.2025.103003

Hassan M. Otifi , Muhammad Faisal Hayat , Ali Akbar , Syeda Sania Zahara , Khalid J. Alzahrani , Fuad M. Alzahrani , Khalaf F. Alsharif

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引用次数: 0

Abstract

Thallium sulphate (TLM) is a highly hazardous metal known to induce severe renal damage. Syringetin (SGN) is a naturally derived polyphenolic compound that demonstrates excellent medicinal properties. This research trial was conducted to determine the nephroprotective ability of SGN to inhibit TLM induced renal toxicity in rats by assessing different parameters including oxidative stress, apoptotic and inflammatory markers as well as histo-morphological parameters. Thirty-two Sprague Dawley rats were apportioned into the control, TLM (6.4 mgkg⁻¹), TLM (6.4 mgkg⁻¹) + SGN (10 mgkg⁻¹) and SGN (10 mgkg⁻¹) alone administered group. Our findings revealed that TLM exposure promoted renal inflammation which was evident by increased mRNA expression of myeloid differentiation primary response 88 (MYD88), toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), high mobility group box1 (HMGB1), tumor necrosis factor- α (TNF-α), receptor for advanced glycation end products (RAGE), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and nuclear factor- kappa B (NF-κB). The concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) were exacerbated while the enzymatic action of heme oxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), & tissue contents of glutathione (GSH) were reduced after TLM intoxication. Serum concentrations of N-Acetylglucosamine (NAG), blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), creatinine, uric acid were observed elevated while a notable reduction was noted in the concentration of creatinine clearance following the dose administration of TLM. The levels of Bcl-2–associated X protein (Bax), cysteine-aspartic acid protease-3 (Caspase-3) & cysteine-aspartic acid protease-9 (Caspase-9) were exacerbated while the concentration of B-cell lymphoma-2 (Bcl-2) was notably suppressed following regimen of TLM. Renal tissues were distorted after TLM administration. In contrast, SGN supplementation notably restored oxidative profile, reduced pro-inflammatory and apoptotic markers as well as improved renal histology.

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紫丁香素通过调控Nrf2/Keap-1、TLR4/HMGB1/RAGE和NF-κB通路改善硫酸铊所致肾功能障碍

硫酸铊（TLM）是一种高度危险的金属，已知会引起严重的肾脏损害。紫丁香素（SGN）是一种天然衍生的多酚类化合物，具有优异的药用性能。本研究通过对氧化应激、细胞凋亡和炎症标志物以及组织形态学参数的评估，来确定SGN对TLM诱导的大鼠肾毒性的保护能力。将32只Sprague Dawley大鼠分为对照组、TLM （6.4 mgkg−1）、TLM (6.4 mgkg−1)+ SGN （10 mgkg−1）组和SGN （10 mgkg−1）单独给药组。我们的研究结果显示，TLM暴露促进肾脏炎症，其明显表现为髓样分化初级反应88 （MYD88）、toll样受体4 （TLR4）、白细胞介素-1β (IL-1β)、高迁移率组box1 （HMGB1）、肿瘤坏死因子-α (TNF-α)、晚期糖基化终产物受体（RAGE）、环氧化酶-2 （COX-2）、白细胞介素-6 （IL-6）和核因子-κB （NF-κB）的mRNA表达增加。活性氧（ROS）和丙二醛（MDA）浓度升高，血红素氧化酶-1 （HO-1）、超氧化物歧化酶（SOD）、谷胱甘肽还原酶（GSR）、过氧化氢酶（CAT）和过氧化氢酶(amp；TLM中毒后组织中谷胱甘肽（GSH）含量降低。给药后血清n -乙酰氨基葡萄糖（NAG）、血尿素氮（BUN）、肾损伤分子-1 （KIM-1）、中性粒细胞明胶酶相关脂载蛋白（NGAL）、肌酐、尿酸浓度升高，肌酐清除率明显降低。bcl -2相关X蛋白（Bax）、半胱氨酸-天冬氨酸蛋白酶-3 （Caspase-3）和amp；半胱氨酸-天冬氨酸蛋白酶-9 （Caspase-9）升高，而b细胞淋巴瘤-2 （Bcl-2）浓度明显抑制。TLM给药后肾脏组织变形。相比之下，补充SGN可显著恢复氧化谱，减少促炎和凋亡标志物，改善肾脏组织学。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.