Alqahtani Leena S, Alosaimi Manal E, Abdel-Rahman Mohamed Amany, Abd-Elhakim Yasmina M, Khamis Tarek, Noreldin Ahmed E, El-Far Ali H, Alotaibi Badriyah S, Hakami Mohammed Ageeli, Dahran Naief, Babteen Nouf A
Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
Front Pharmacol. 2024 Jul 17;15:1413844. doi: 10.3389/fphar.2024.1413844. eCollection 2024.
Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health. This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10 mg/kg b.wt.), ACR (20 mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A. ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.
肾脏功能的任何紊乱都可能对整体健康产生连锁反应。了解像丙烯酰胺（ACR）这样的热生成毒物如何影响肾脏组织，对于认识其对全身健康的更广泛影响至关重要。在一项初步研究中，本研究调查了ACR诱导的肾损伤机制，特别关注miR - 21a - 5p/纤维化和miR - 122 - 5p/炎症信号通路通过靶向Timp - 3和TP53蛋白的调节作用。此外，在一项为期60天的实验中评估了肾功能、氧化状态、蛋白质谱以及肾脏生物标志物（Timp - 1、Keap - 1、Kim - 1、P53、TNF -α、Bax和Caspase3）的表达。该检查还进一步扩展以探索绿色合成的氧化锌纳米颗粒（ZNO - MONPs）的潜在保护作用。建立了一个包括对照组、ZNO - MONPs（10毫克/千克体重）、ACR（20毫克/千克体重）和ZNO - MONPs + ACR的四组实验，涵盖生化、组织学和分子水平。该研究进一步研究了ZNO和MONPs使caspase - 3、Keap - 1、Kim - 1和TNFRS - 1A失活的蛋白质结合能力。ZNO - MONPs显著减轻了ACR诱导的肾组织损伤，血清肌酐、尿酸、白蛋白和氧化应激标志物升高证明了这一点。生化测试、基因表达以及显微镜下凋亡细胞核的存在揭示了ACR诱导的氧化应激、细胞凋亡和炎症。此外，分子对接揭示了ACR - BCL - 2与谷胱甘肽合成酶之间的结合亲和力，阐明了ACR诱导肾损伤的潜在机制。值得注意的是，ZNO - MONPs显示出对ACR诱导损伤的保护潜力。用ACR + ZNO - MONPs治疗的大鼠肾组织中的锌水平在ACR暴露大鼠中显著恢复。总之，本研究证实了ZNO - MONPs在减轻ACR诱导的肾组织功能紊乱、氧化应激、炎症和细胞凋亡方面的功效。这些发现揭示了绿色合成纳米材料潜在的肾脏保护活性，为对抗ACR诱导的肾损伤的新型治疗方法提供了见解。
