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通过调节Nrf2/Keap1通路研究紫苏亭对百草枯诱导的大鼠肾毒性的改善潜力:炎症、凋亡及组织病理学评估

Ameliorative Potential of Sudachitin Against Paraquat Induced Renal Toxicity in Rats Via Regulating Nrf2/Keap1 Pathway: An Inflammatory, Apoptotic and Histopathological Assessment.

作者信息

Faisal Hayat Muhammad, Bibi Marrium, Batool Moazama, Eman Rimsha, Hamdi Hamida, Umar Ijaz Muhammad

机构信息

Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, 38040, Pakistan.

Department of Zoology, Govt. College Women University, Sialkot, Pakistan.

出版信息

Chem Biodivers. 2025 Jan;22(1):e202401656. doi: 10.1002/cbdv.202401656. Epub 2024 Nov 12.

DOI:10.1002/cbdv.202401656
PMID:39307685
Abstract

Paraquat (PQ) is a noxious herbicide which is well known for its adverse effects on vital organs including kidneys. Sudachitin (SCN) is a plant derived flavone that is obtained from Citrus sudachi and demonstrates a range of pharmacological potentials. This investigation was executed to assess the protective effects of SCN to counteract PQ instigated renal damage in albino rats (Rattus norvegicus). Twenty-four rats were apportioned in 4 different groups i. e., control group, PQ (5 mg/kg) intoxicated group, PQ (5 mg/kg)+SCN (20 mg/kg) cotreated group and SCN (20 mg/kg) only administrated group. Our findings revealed that exposure to PQ reduced the expressions of Nrf2 (nuclear factor erythroid 2-related factor 2) and its cytoprotective genes while escalating the expression of keap1. Furthermore, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), heme-oxygenase-1 (HO-1) and glutathione (GSH) contents while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Moreover, PQ exposure significantly increased the levels of neutrophil gelatinous-associated lipocalin (NGAL), urea, kidney injury molecule-1(KIM-1) as well as creatine while reducing creatine clearance. Additionally, PQ upregulated the levels of inflammatory markers including interleukin-6 (IL-6), tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin 1beta (IL-1β), and cyclo-oxygenase-2 (COX-2). Moreover, PQ administration upregulated the expression of Bax (Bcl-2-associated X protein) and (cysteine-aspartic acid protease) Caspase-3 while downregulating the expressions of (B-cell lymphoma 2 protein) Bcl-2. Besides, PQ exposure prompted various histopathological damages in renal tissues. Nonetheless, SCN substantially restored aforementioned alterations in the renal tissues owing to its anti-oxidative, anti-inflammatory and anti-apoptotic potential.

摘要

百草枯(PQ)是一种有害除草剂,因其对包括肾脏在内的重要器官的不良影响而闻名。须崎亭(SCN)是一种从植物中提取的黄酮类化合物,从日本须崎柑橘中获得,具有一系列药理潜力。本研究旨在评估SCN对减轻白化大鼠(褐家鼠)中PQ诱发的肾损伤的保护作用。将24只大鼠分为4个不同的组,即对照组、PQ(5 mg/kg)中毒组、PQ(5 mg/kg)+SCN(20 mg/kg)联合治疗组和仅给予SCN(20 mg/kg)组。我们的研究结果表明,暴露于PQ会降低Nrf2(核因子红细胞2相关因子2)及其细胞保护基因的表达,同时增加keap1的表达。此外,PQ中毒会降低超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GSR)、血红素加氧酶-1(HO-1)的活性和谷胱甘肽(GSH)含量,同时增加丙二醛(MDA)和活性氧(ROS)水平。此外,PQ暴露显著增加中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、尿素、肾损伤分子-1(KIM-1)以及肌酸水平,同时降低肌酐清除率。此外,PQ上调包括白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、白细胞介素1β(IL-1β)和环氧化酶-2(COX-2)在内的炎症标志物水平。此外,PQ给药上调Bax(Bcl-2相关X蛋白)和(半胱天冬酶)Caspase-3的表达,同时下调(B细胞淋巴瘤2蛋白)Bcl-2的表达。此外,PQ暴露导致肾组织出现各种组织病理学损伤。尽管如此,由于其抗氧化、抗炎和抗凋亡潜力,SCN显著恢复了肾组织中的上述变化。

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