Ragab Tamer I M, Zoheir Khairy M A, Mohamed Nadia A, El Gendy Abd El-Nasser G, Abd-ElGawad Ahmed M, Abdelhameed Mohamed F, Farrag Abdel Razik H, Elshamy Abdelsamed I
Chemistry of Natural and Microbial Products Department, National Research Centre, Dokki, Giza 12622, Egypt.
Cell Biology Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza 12622, Egypt.
Heliyon. 2022 Mar 25;8(3):e09198. doi: 10.1016/j.heliyon.2022.e09198. eCollection 2022 Mar.
Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.
顺铂（Cisp）是一种广泛应用于癌症治疗的化疗药物。肾毒性是使用该药物最常见的副作用之一。香芹酚（CV）是药用植物精油和提取物中常见的天然化合物，具有强大的体内和体外生物活性。这项工作得以扩展，以实现研究CV及其纳米乳剂作为细胞保护药物对白化大鼠顺铂诱导的肾毒性的保护潜力这一目标。CV纳米乳剂由亲水性表面活性剂聚山梨酯80（吐温80）和去离子水制备而成。所制备纳米乳剂的颗粒分布的透射电镜图像主要呈球形，粒径在14至30纳米之间变化。此外，给予顺铂导致血液和血清中尿素和肌酐水平升高。尿素和肌酐水平的这些升高进而导致氧化应激紊乱以及血清中高敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平升高。同时，观察到肾组织的组织病理学变化。通过用CV纳米乳剂治疗，这些变化恢复正常。使用qRT-PCR测量了肾组织中肾毒性相关基因包括半乳糖凝集素3（LGALS3）、血管内皮生长因子（VEGF）和窖蛋白1（CAV1）的表达水平。结果显示，与其他治疗组相比，仅顺铂治疗组中LGALS3、VEGF和CAV1基因的表达显著高度增加。而与顺铂治疗的大鼠相比，顺铂+CV治疗组中这些基因的表达显著降低（P<0.001）。此外，顺铂+纳米CV治疗组与阴性对照组和单独纳米乳剂组之间无显著差异，但不显著。此外，蛋白质分析的蛋白质印迹结果显示，与其他组相比，LGALS3和CAV1仅在顺铂+CV治疗组中高表达。顺铂+纳米CV治疗的动物与阴性对照组在mRNA和蛋白质表达方面均无显著差异。基于这些结果，将CV与海藻酸钙结合；形成了更稳定的胶囊，使得微胶囊中形成双壁。这些结果支持了CV及其纳米乳剂作为抗顺铂肾毒性细胞保护剂的治疗效果。
