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姜黄素在重塑鱼肾脏氧化还原动力学中的作用:激活NRF2作为对抗铜诱导的肾病的一种策略。

Curcumin's role in reshaping the redox dynamics of fish kidneys: NRF2 activation as a strategy against copper-induced nephropathy.

作者信息

Trivedi Abha, Saxena Vaishnavi, Bakhasha Jumman, Arya Neeti, Yadav Kamlesh K, Srivastava Alok, Trivedi Sunil P, Banaee Mahdi, Sopjani Mentor, Faggio Caterina

机构信息

Toxicogenomics Laboratory, Department of Animal Science, M.J.P. Rohilkhand University, Bareilly, 243006, India.

Department of Zoology, Government Degree College, Bakkha Kheda, Unnao, 209801, India.

出版信息

Fish Physiol Biochem. 2025 May 7;51(3):94. doi: 10.1007/s10695-025-01506-x.

DOI:10.1007/s10695-025-01506-x
PMID:40332669
Abstract

From essential to harmful, excess copper compromises aquatic vitality. Curcumin, a potent antioxidant bioactive, counteracts heavy metal toxicity. This study examines its role in modulating the NRF2-KEAP1 pathway to boost antioxidant defenses and mitigate apoptosis in kidneys of Channa punctatus exposed to environmentally relevant Copper concentrations (ERCC). 180 fully habituated fish were categorized into six groups: Group 1 served as control, Group 2 was treated with 3 mg/L Curcumin, Group 3 was exposed to ERCC (0.85 mg/L Copper), while Group 4, Group 5 and Group 6 received co-exposure to ERCC along with the escalating Curcumin concentrations of 1 mg/L, 2 mg/L, and 3 mg/L, respectively, over periods of 15, 30, 45, 60, and 75 days. Biochemical assays were conducted to evaluate oxidative stress markers (Reactive oxygen species, reduced glutathione, glutathione peroxidase, and lipid peroxidation), kidney damage indicators (creatinine), and genotoxicity (micronuclei). Additionally, transcriptional profiling assessed mRNA levels of apoptosis-related factors (p53, bax, apaf1, cas9, cas3 and bcl2), while histopathological examinations revealed changes in renal architecture. Molecular docking analysis confirmed Curcumin's strong binding affinity to KEAP1, providing insights into its role in activating the NRF2-KEAP1 pathway. The results indicated that Curcumin significantly (p < 0.05) reduced Copper-induced oxidative stress, improved antioxidant defenses, suppressed genotoxicity, modulated apoptosis, and maintained renal tissue integrity. These findings validate curcumin's potential in effectively combating copper toxicity in aquaculture, paving the way for enhanced fish health and improved food safety.

摘要

从必需元素变为有害元素,过量的铜会损害水生生物的活力。姜黄素是一种强大的抗氧化生物活性物质,可对抗重金属毒性。本研究考察了姜黄素在调节NRF2-KEAP1通路中的作用,以增强抗氧化防御能力,并减轻暴露于环境相关铜浓度(ERCC)下的斑鳢肾脏中的细胞凋亡。180条完全适应环境的鱼被分为六组:第1组作为对照组,第2组用3mg/L姜黄素处理,第3组暴露于ERCC(0.85mg/L铜),而第4组、第5组和第6组在15天、30天、45天、60天和75天的时间内,分别接受ERCC与浓度逐渐升高的1mg/L、2mg/L和3mg/L姜黄素的共同暴露。进行了生化分析,以评估氧化应激标志物(活性氧、还原型谷胱甘肽、谷胱甘肽过氧化物酶和脂质过氧化)、肾脏损伤指标(肌酐)和遗传毒性(微核)。此外,转录谱分析评估了凋亡相关因子(p53、bax、apaf1、cas9、cas3和bcl2)的mRNA水平,而组织病理学检查揭示了肾脏结构的变化。分子对接分析证实了姜黄素与KEAP1具有很强的结合亲和力,这为其在激活NRF2-KEAP1通路中的作用提供了见解。结果表明,姜黄素显著(p<0.05)降低了铜诱导的氧化应激,改善了抗氧化防御能力,抑制了遗传毒性,调节了细胞凋亡,并维持了肾组织的完整性。这些发现验证了姜黄素在有效对抗水产养殖中铜毒性方面的潜力,为增强鱼类健康和改善食品安全铺平了道路。

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本文引用的文献

1
DNA Damage, Cell Death, and Alteration of Cell Proliferation Insights Caused by Copper Oxide Nanoparticles Using a Plant-Based Model.使用植物模型对氧化铜纳米颗粒引起的DNA损伤、细胞死亡及细胞增殖变化的见解
Biology (Basel). 2024 Oct 9;13(10):805. doi: 10.3390/biology13100805.
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Remission of copper-induced liver injury through the PXR/NF-kB signaling pathway: The effects of dietary curcumin supplementation in largemouth bass (Micropterus salmoides).通过 PXR/NF-κB 信号通路缓解铜诱导的肝损伤:膳食姜黄素补充对大口黑鲈(Micropterus salmoides)的影响。
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Deadly excess copper.
致命的过量铜。
Redox Biol. 2024 Sep;75:103256. doi: 10.1016/j.redox.2024.103256. Epub 2024 Jun 28.
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Copper redox state in cells and aquatic organisms: Implication for toxicity.细胞和水生生物中的铜氧化还原状态:对毒性的影响。
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Natural products as non-covalent and covalent modulators of the KEAP1/NRF2 pathway exerting antioxidant effects.天然产物作为 KEAP1/NRF2 通路的非共价和共价调节剂,发挥抗氧化作用。
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Copper overload induces apoptosis and impaired proliferation of T cell in zebrafish.铜过载诱导斑马鱼 T 细胞凋亡和增殖障碍。
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The Schiff base hydrazine copper(II) complexes induce apoptosis by P53 overexpression and prevent cell migration through protease-independent pathways.席夫碱肼合铜(II)配合物通过 P53 过表达诱导细胞凋亡,并通过非蛋白酶依赖途径抑制细胞迁移。
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