Nanotechnology has proven advantageous in numerous scientific applications, one being to enhance the delivery of chemotherapeutic agents. This present study aims to evaluate the mechanisms underlying the chemopreventive action of naringin–dextrin nanocomposites (Nar-Dx-NCs) against diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced lung carcinogenesis in male Wistar rats. DEN was administered intraperitoneally (i.p.) (150 mg/kg/week) for two weeks, followed by the oral administration of 2AAF (20 mg/kg) four times a week for three weeks. Rats receiving DEN/2AAF were concurrently treated with naringin or Nar-Dx-NCs orally at a dose of 10 mg/kg every other day for 24 weeks. Naringin and Nar-Dx-NCs treatments prevented the formation of tumorigenic cells within the alveoli of rats exposed to DEN/2AAF. These findings were associated with a significant decrease in lipid peroxidation, upregulation of antioxidant enzyme (glutathione peroxidase and superoxide dismutase) activity, and enhanced glutathione and nuclear factor erythroid 2–related factor 2 expression in the lungs. Naringin and Nar-Dx-NCs exerted anti-inflammatory actions manifested by a decrease in lung protein expression of tumor necrosis factor-α and interleukin-1β and mRNA expression of interleukin-6, interferon-γ, nuclear factor-κB, and inducible nitric oxide synthase, with a concurrent increase in interleukin-10 expression. The anti-inflammatory effect of Nar-Dx-NCs was more potent than naringin. Regarding the effect on apoptosis, both naringin and Nar-Dx-NCs significantly reduced Bcl-2 and increased Bax and P53 expressions. Moreover, naringin or Nar-Dx-NCs induced a significant decrease in the expression of the proliferator marker, Ki-67, and the effect of Nar-Dx-NCs was more marked. In conclusion, Nar-Dx-NCs improved naringin’s preventive action against DEN/2AAF-induced lung cancer and exerted anticarcinogenic effects by suppressing oxidative stress and inflammation and improving apoptotic signal induction and propagation.
纳米技术在众多科学应用中已展现出显著优势，其中一项重要应用是增强化疗药物的递送效率。本研究旨在探讨柚皮苷-糊精纳米复合材料（Nar-Dx-NCs）对二乙基亚硝胺（DEN）/2-乙酰氨基芴（2AAF）诱导的雄性Wistar大鼠肺癌发生的化学预防作用机制。实验通过腹腔注射DEN（150毫克/千克/周）持续两周，随后每周四次口服2AAF（20毫克/千克）持续三周。在DEN/2AAF处理期间，大鼠每隔一天口服10毫克/千克的柚皮苷或Nar-Dx-NCs，持续24周。结果显示，柚皮苷与Nar-Dx-NCs处理能有效抑制DEN/2AAF暴露大鼠肺泡内肿瘤细胞的生成。这一作用与肺部脂质过氧化水平显著降低、抗氧化酶（谷胱甘肽过氧化物酶和超氧化物歧化酶）活性上调、以及谷胱甘肽和核因子E2相关因子2表达增强密切相关。两种处理均表现出抗炎作用，具体表现为肺组织中肿瘤坏死因子-α和白细胞介素-1β的蛋白表达水平下降，白细胞介素-6、干扰素-γ、核因子-κB及诱导型一氧化氮合酶的mRNA表达降低，同时白细胞介素-10表达升高，且Nar-Dx-NCs的抗炎效果优于柚皮苷。在凋亡调控方面，柚皮苷与Nar-Dx-NCs均能显著降低Bcl-2表达，同时提升Bax和P53表达。此外，两者均能显著抑制增殖标志物Ki-67的表达，其中Nar-Dx-NCs的作用更为显著。综上所述，Nar-Dx-NCs通过增强柚皮苷对DEN/2AAF诱导肺癌的预防作用，并借助抑制氧化应激与炎症反应、促进凋亡信号传导等机制，发挥出显著的抗癌效应。
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