Laboratory of Experimental Pathophysiology (LAFEx), Department of Biological Sciences and Center of Research in Biological Sciences, Federal University of Ouro Preto (UFOP), 35400-000 Ouro Preto, Minas Gerais, Brazil.
Laboratory of Immunobiology of Inflammation (LABIIN), Department of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), 35400-000 Ouro Preto, Minas Gerais, Brazil.
Int Immunopharmacol. 2023 Aug;121:110454. doi: 10.1016/j.intimp.2023.110454. Epub 2023 Jun 8.
Lycopene is a natural compound with one of the highest antioxidant activities. Its consumption is associated with lower risks in lung cancer and chronic obstructive pulmonary disease, for example. Experimentally, a murine model demonstrated the ingestion of lycopene, which reduced the damage in lungs caused by cigarette smoke. Since lycopene is highly hydrophobic, its formulations in supplements and preparations for laboratory assays are based on oils, additionally, bioavailavility is low. We developed a lycopene layered double hydroxide (Lyc-LDH) composite, which is capable of transporting lycopene aqueous media. Our objective was to evaluate the cytotoxicity of Lyc-LDH and the intra-cellular production of reactive oxygen species (ROS) in J774A.1 cells. Also, in vivo assays were conducted with 50 male C57BL/6 mice intranasally treated with Lyc-LDH 10 mg/kg (LG10), Lyc-LDH 25 mg/kg (LG25) and Lyc-LDH 50 mg/kg (LG50) during five days compared against a vehicle (VG) and control (CG) group. The blood, bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed. The results revealed that Lyc-LDH composite attenuated intracellular ROS production stimulated with lipopolysacharide. In BALF, the highest doses of Lyc-LDH (LG25 and LG50) promoted influx of macrophages, lymphocytes, neutrophils and eosinophils compared to CG and VG. Also, LG50 increased the levels of IL-6 and IL-13, and promoted the redox imbalance in the pulmonary tissue. On the contrary, low concentrations did not produce significative effects. In conclusion, our results suggest that intranasal administration of high concentrations of Lyc-LDH induces inflammation as well as redox status changes in the lungs of healthy mice, however, results with low concentrations open a promising way to study LDH composites as vehicles for intranasal administration of antioxidant coadjuvants.
番茄红素是一种具有最高抗氧化活性的天然化合物。例如,其摄入与肺癌和慢性阻塞性肺疾病的风险降低有关。在实验中,鼠模型表明摄入番茄红素可减少香烟烟雾对肺部的损害。由于番茄红素具有很强的疏水性,因此其在补充剂和实验室制剂中的配方都基于油,此外,生物利用度也很低。我们开发了一种番茄红素层状双氢氧化物(Lyc-LDH)复合材料,能够在水性介质中输送番茄红素。我们的目的是评估 Lyc-LDH 的细胞毒性以及 J774A.1 细胞内活性氧(ROS)的产生。此外,还对 50 只雄性 C57BL/6 小鼠进行了体内试验,这些小鼠在五天内通过鼻腔给予 Lyc-LDH10mg/kg(LG10)、Lyc-LDH25mg/kg(LG25)和 Lyc-LDH50mg/kg(LG50),并与载体(VG)和对照(CG)组进行了比较。分析了血液、支气管肺泡灌洗液(BALF)和肺组织。结果表明,Lyc-LDH 复合体能减轻脂多糖刺激的细胞内 ROS 产生。在 BALF 中,与 CG 和 VG 相比,Lyc-LDH 的最高剂量(LG25 和 LG50)促进了巨噬细胞、淋巴细胞、中性粒细胞和嗜酸性粒细胞的流入。此外,LG50 增加了 IL-6 和 IL-13 的水平,并促进了肺组织中的氧化还原失衡。相反,低浓度没有产生显著的效果。总之,我们的结果表明,鼻腔给予高浓度的 Lyc-LDH 会导致健康小鼠肺部炎症以及氧化还原状态的改变,然而,低浓度的结果为研究 LDH 复合材料作为鼻腔给予抗氧化佐剂的载体开辟了一条有前途的途径。