Biotechnology Department, Faculty of Science, Cairo University, Giza, Egypt.
Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), Giza, Egypt.
Sci Rep. 2023 Sep 30;13(1):16424. doi: 10.1038/s41598-023-43546-4.
Liver is an important organ that carries out major important functions including the detoxification of harmful chemicals. Numerous studies have lately focused on the impact of various substances, such as chemical pollutants and pharmaceutical drugs, on the liver. Melatonin (Mel) has been reported for the protection against liver injury. In order to enhance Mel therapeutic benefits and prevent any potential negative effects, Mel has to be delivered to the injured liver. Therefore, the goal of the current investigation was to create Mel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Mel-PLGA NPs) to alleviate carbon tetrachloride (CCL4)-induced liver damage in male Sprague Dawley rats. The prepared Mel-PLGA NPs were physically characterized to determine its size and charge. Moreover, Mel-PLGA NPs were examined, in vitro, to determine its antioxidant, anticoagulant, anti-inflammatory and cytotoxicity effects before being used in vivo. The effect of NPs on liver injury was evaluated through biochemical, immunological, histopathological examination and flow cytometry technique. Mel-PLGA NPs were smooth and spherical with no signs of aggregation and have in vitro antioxidant, anti-inflammatory and anticoagulant effects. NPs varied in size from 87 to 96 nm in transmission electron microscope images, while their hydrodynamic diameter was 41 nm and their zeta potential was -6 mV. Mel-PLGA NPs had encapsulation efficiency (EE%) and drug loading (DL%) of 59.9 and 12.5%, respectively. Treatment with Mel-PLGA NPs ameliorated all histopathological changes, in liver sections, that resulted from CCL4 administration; where, liver sections of treated groups were similar to those of healthy control GI. NPs administration were superior to free Mel and reversed the elevated levels of liver function enzymes, inflammatory cytokines and matrix metalloproteinases to their normal levels. Moreover, liver sections of groups treated with NPs showed negative immunostaining for nuclear factor-κB (NF-κB) and C-reactive protein indicating their anti-inflammatory behavior. Mel-PLGA NPs significantly protected liver from the toxicity of CCL4. The effective dose of NPs was 5 mg/kg indicating a reduction in the required Mel dose and its associated adverse effects.
肝脏是一个重要的器官，具有多种重要功能，包括解毒有害化学物质。最近，许多研究都集中在各种物质（如化学污染物和药物）对肝脏的影响上。褪黑素（Mel）已被报道具有保护肝脏免受损伤的作用。为了提高 Mel 的治疗效果并防止任何潜在的副作用，必须将 Mel 递送到受损的肝脏。因此，本研究的目的是制备载有褪黑素的聚（乳酸-共-乙醇酸）（PLGA）纳米粒（Mel-PLGA NPs），以减轻雄性 Sprague Dawley 大鼠四氯化碳（CCL4）诱导的肝损伤。对制备的 Mel-PLGA NPs 进行物理特性分析，以确定其粒径和电荷。此外，还在体外研究了 Mel-PLGA NPs 的抗氧化、抗凝、抗炎和细胞毒性作用，然后再在体内使用。通过生化、免疫、组织病理学检查和流式细胞术技术评估 NPs 对肝损伤的影响。Mel-PLGA NPs 呈光滑球形，无聚集迹象，具有体外抗氧化、抗炎和抗凝作用。透射电子显微镜图像中 NPs 的粒径为 87-96nm，水动力直径为 41nm，Zeta 电位为-6mV。Mel-PLGA NPs 的包封效率（EE%）和载药量（DL%）分别为 59.9%和 12.5%。Mel-PLGA NPs 治疗可改善 CCL4 给药引起的肝组织切片的所有组织病理学变化；其中，治疗组的肝切片与健康对照组 GI 的肝切片相似。NPs 给药优于游离 Mel，并将升高的肝功能酶、炎症细胞因子和基质金属蛋白酶水平恢复至正常水平。此外，用 NPs 治疗的肝组织切片 NF-κB（NF-κB）和 C 反应蛋白的免疫染色为阴性，表明其具有抗炎作用。Mel-PLGA NPs 可显著保护肝脏免受 CCL4 的毒性作用。NPs 的有效剂量为 5mg/kg，表明降低了所需 Mel 剂量及其相关的不良反应。
