罗氟司特和纳米硒粒子通过调节抗氧化和细胞凋亡途径对顺铂产生的肾毒性的综合影响

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2024-10-18 DOI:10.1016/j.jtemb.2024.127555

Nashwa Barakat , Ehab Ismail , Faten Zahran

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引用次数: 0

摘要

目的：本研究旨在探讨服用罗氟司特（ROF）和纳米硒颗粒（SeNPs）对顺铂（Cis）诱导的肾毒性的潜在协同作用：将 50 只雄性大鼠分为 5 组：对照组：给动物注射 0.9 % 的生理盐水。顺铂组：动物注射单剂量 6 毫克/千克。ROF 组：大鼠每天口服 1.2 毫克/千克，连续 11 天。SeNPs 组：动物每天口服 0.5 毫克/千克 ROF，共 11 天。ROF + SeNPs 组在接受顺式注射 11 天后同时给药。动物分别在第 5 天和第 11 天被处死，并在第 5 天和第 11 天采集尿液和血液样本进行化学分析，同时采集肾脏样本进行分子、组织学和免疫组化研究：结果：与对照组相比，顺式组的血清肌酐、血尿素氮（BUN）和总蛋白水平升高（P < 0.05）。而在 5 天和 11 天后，ROF 和 SeNPs 的组合能显著降低这些数值（P < 0.05）。此外，Cis 通过提高 MDA 水平和抑制 SOD、GSH 和 CAT 的活性引起肾脏氧化应激。同样，在 11 天后，ROF 和 SeNPs 也能调节这些效应（p < 0.05）。此外，与顺式组相比，同时给予 ROF 和 SeNPs 11 天后，HO-1、Nrf2 和 Bcl2 的表达量显著增加，而 BAX 和 IL-6 的表达量则有所减少（P < 0.05）：研究表明，ROF 和 SeNPs 在减轻 Cis 引起的病理改变方面具有显著的治疗潜力。

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The integrated effect of roflumilast and selenium nanoparticles on nephrotoxicity generated by cisplatin through the regulation of the antioxidant and apoptotic pathways

Aim

The current investigations aimed to investigate the potential synergistic effect of Roflumilast (ROF) and Selenium nanoparticles (SeNPs) administration on Cisplatin (Cis) -induced nephrotoxicity.

Materials and methods

Fifty male rats were divided into five groups; Control group: animals were administered 0.9 % saline solution. Cis group: animals were injected with a single dose of 6 mg/kg. ROF group: Rats received a dosage of 1.2 mg/kg orally daily for 11 days. SeNPs group: animals orally received 0.5 mg/kg of ROF daily for 11 days. The ROF + SeNPs group was administered both after receiving a Cis injection for 11 days. Animals were sacrificed at 5 and 11 days, and the urine and blood samples were collected on day 5 and day 11 for chemical analysis, while kidney samples were obtained for molecular, histological, and immunohistochemical studies.

Results

The levels of serum creatinine, Blood urea nitrogen (BUN), and total protein were elevated in the Cis group compared to the control group (p < 0.05). While the combination of ROF and SeNPs dramatically decreased these values after 5 and 11 days (p < 0.05). In addition, Cis caused renal oxidative stress by elevating MDA levels and suppressing the activities of SOD, GSH, and CAT. Similarly, these effects were modulated by ROF and SeNPs after 11 days (p < 0.05). Furthermore, the concurrent administration of ROF and SeNPs resulted in a significant increase in the expression of HO-1, Nrf2, and Bcl2, while decreasing the expression of BAX and IL-6 compared to the Cis group after 11 days (P < 0.05).

Conclusion

The study showed that both ROF and SeNPs had significant therapeutic potential in reducing the pathological alterations caused by Cis.

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.