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Protective effect of gallic acid and gallic acid-loaded Eudragit-RS 100 nanoparticles on cisplatin-induced mitochondrial dysfunction and inflammation in rat kidney.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.bbadis.2020.165911
Mohammad Amin Dehghani 1 , Nader Shakiba Maram 2 , Eskandar Moghimipour 3 , Layasadat Khorsandi 4 , Morteza Atefi Khah 5 , Masoud Mahdavinia 1
Affiliation  

Cisplatin is used as a chemotherapy drug in the treatment of various types of cancer. Mitochondrial dysfunction, oxidative stress and inflammation have been identified as major mechanisms of cisplatin nephrotoxicity. The present study investigated the protective effects of pure gallic acid and nanoparticle gallic acid nanoparticles (nano-gallic acid) on cisplatin induced nephrotoxicity. Nano-gallic acid was prepared by double emulsions-solvent evaporation technique using Eudragit RS 100 polymer and polyvinyl alcohol as carrier. Then, the physicochemical characterization of the nanoparticles was examined. In the present study, renal mitochondria were isolated using different centrifugal methods. Our data indicated that the doses of 50 and 100 mg/kg gallic acid and 10 mg/kg nano-gallic acid significantly decreased mitochondrial reactive oxygen species (ROS) formation, mitochondrial membrane damage (ΔΨm), mitochondrial malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and significantly increased mitochondrial glutathione (GSH), mitochondrial superoxide dismutase (MnSOD), mitochondrial glutathione peroxidase (GPX) and mitochondrial catalase compared to the cisplatin treated group. Histopathological studies also confirmed biochemical tests. Finally, our results confirmed that the pure gallic acid and its nanoparticle improved renal oxidative stress, inflammation and mitochondrial dysfunction in acute nephrotoxicity induced by cisplatin in rat. Nano-gallic acid (10 mg/kg) was selected as the most effective dose. The findings of this study showed the superiority of nano-gallic acid against pure gallic acid. In conclusion, nano-gallic acid-loaded Eudragit-RS 100 as a novel antioxidant can be considered in the treatment of renal complications of cisplatin.



中文翻译:

没食子酸和没食子酸的Eudragit-RS 100纳米颗粒对顺铂诱导的大鼠肾脏线粒体功能障碍和炎症的保护作用。

顺铂用作治疗各种类型癌症的化学疗法药物。线粒体功能障碍,氧化应激和炎症已被确认为顺铂肾毒性的主要机制。本研究调查了纯没食子酸和纳米没食子酸纳米颗粒(纳米没食子酸)对顺铂诱导的肾毒性的保护作用。以Eudragit RS 100聚合物和聚乙烯醇为载体,通过双乳液-溶剂蒸发技术制备了纳米没食子酸。然后,检查了纳米颗粒的理化特性。在本研究中,使用不同的离心方法分离肾线粒体。我们的数据表明,50和100 mg / kg没食子酸和10 mg / kg纳米没食子酸的剂量显着降低了线粒体活性氧(ROS)的形成,线粒体膜损伤(ΔΨm),线粒体丙二醛(MDA),肿瘤坏死与顺铂治疗组相比,α因子(TNF-α),白介素6(IL-6)和线粒体谷胱甘肽(GSH),线粒体超氧化物歧化酶(MnSOD),线粒体谷胱甘肽过氧化物酶(GPX)和线粒体过氧化氢酶显着增加。组织病理学研究也证实了生化检查。最后,我们的结果证实了纯没食子酸及其纳米颗粒改善了顺铂在大鼠急性肾毒性中的肾脏氧化应激,炎症和线粒体功能障碍。纳米没食子酸(10 mg / kg)被选为最有效剂量。这项研究的结果表明,纳米没食子酸比纯没食子酸具有优越性。综上所述,可以考虑将纳米没食子酸Eudragit-RS 100作为新型抗氧化剂用于治疗顺铂的肾脏并发症。

更新日期:2020-08-21
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