Vesicular (liposomal and nanoparticulated) delivery of curcumin: a comparative study on carbon tetrachloride-mediated oxidative hepatocellular damage in rat model.
Vesicular (liposomal and nanoparticulated) delivery of curcumin: a comparative study on carbon tetrachloride-mediated oxidative hepatocellular damage in rat model.
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DOI：
10.2147/ijn.s101886
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发表时间：
2016
影响因子：
8
通讯作者：
Ali N
中科院分区：
文献类型：
--
作者：
Choudhury ST;Das N;Ghosh S;Ghosh D;Chakraborty S;Ali N
肝脏在生物转化和释放外源性物质方面发挥着至关重要的作用，因此很容易受到其毒性的影响。短期给予四氯化碳（CCl4）通过增强细胞活性氧（ROS）水平、促进线粒体功能障碍和诱导细胞凋亡而引起肝脏炎症。姜黄素因其抗氧化和抗炎特性而被广泛接受，可被认为是对抗肝毒性的有效治疗剂。然而，由于其不溶于水，其治疗效果受到影响。姜黄素的囊泡递送可以解决这一限制，从而提高其有效性。在这项研究中，观察到姜黄素的脂质体和纳米颗粒制剂都可以通过预防细胞氧化应激来显着提高其抗肝毒性的功效。然而，最好的保护可以通过聚合物纳米颗粒介导的姜黄素递送来获得。线粒体在 ROS 稳态和细胞生存能力中发挥着关键作用。除了维持细胞 ROS 水平外，纳米颗粒姜黄素还显着 (P<0.0001) 增加细胞抗氧化酶，避免线粒体过度破坏，并防止 CCl4 治疗大鼠的总体肝损伤。该疗法不仅可以防止细胞受到氧化损伤，还可以阻止内在的凋亡途径。此外，它还减少了组织病理学分析中明显的肝细胞脂肪变化、中心区坏死和门静脉炎症。总之，与脂质体姜黄素相比，负载姜黄素的聚合物纳米颗粒在预防 CCl4 诱导的氧化应激介导的肝细胞损伤方面更有效，因此可以被认为是一种有效的治疗策略。
The liver plays a vital role in biotransforming and extricating xenobiotics and is thus prone to their toxicities. Short-term administration of carbon tetrachloride (CCl4) causes hepatic inflammation by enhancing cellular reactive oxygen species (ROS) level, promoting mitochondrial dysfunction, and inducing cellular apoptosis. Curcumin is well accepted for its antioxidative and anti-inflammatory properties and can be considered as an effective therapeutic agent against hepatotoxicity. However, its therapeutic efficacy is compromised due to its insolubility in water. Vesicular delivery of curcumin can address this limitation and thereby enhance its effectiveness. In this study, it was observed that both liposomal and nanoparticulated formulations of curcumin could increase its efficacy significantly against hepatotoxicity by preventing cellular oxidative stress. However, the best protection could be obtained through the polymeric nanoparticle-mediated delivery of curcumin. Mitochondria have a pivotal role in ROS homeostasis and cell survivability. Along with the maintenance of cellular ROS levels, nanoparticulated curcumin also significantly (P<0.0001) increased cellular antioxidant enzymes, averted excessive mitochondrial destruction, and prevented total liver damage in CCl4-treated rats. The therapy not only prevented cells from oxidative damage but also arrested the intrinsic apoptotic pathway. In addition, it also decreased the fatty changes in hepatocytes, centrizonal necrosis, and portal inflammation evident from the histopathological analysis. To conclude, curcumin-loaded polymeric nanoparticles are more effective in comparison to liposomal curcumin in preventing CCl4-induced oxidative stress–mediated hepatocellular damage and thereby can be considered as an effective therapeutic strategy.