Mohamed Eman E, Ahmed Osama M, Zoheir Khairy M A, El-Shahawy Ahmed A G, Tamur Shadi, Shams Anwar, Burcher Jack T, Bishayee Anupam, Abdel-Moneim Adel
Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt.
Cell Biology Department, Biotechnology Research Institute, National Research Centre, Cairo 12622, Egypt.
Cancers (Basel). 2023 Oct 22;15(20):5102. doi: 10.3390/cancers15205102.
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.
纳米技术已在众多科学应用中证明具有优势，其中之一是增强化疗药物的递送。本研究旨在评估柚皮苷 - 糊精纳米复合材料（Nar - Dx - NCs）对雄性Wistar大鼠二乙基亚硝胺（DEN）/ 2 - 乙酰氨基芴（2AAF）诱导的肺癌发生的化学预防作用的潜在机制。腹腔注射（i.p.）DEN（150 mg/kg/周），持续两周，随后每周口服2AAF（20 mg/kg）四次，持续三周。接受DEN/2AAF的大鼠同时每隔一天口服10 mg/kg剂量的柚皮苷或Nar - Dx - NCs，持续24周。柚皮苷和Nar - Dx - NCs处理可预防暴露于DEN/2AAF的大鼠肺泡内致瘤细胞的形成。这些发现与脂质过氧化显著降低、抗氧化酶（谷胱甘肽过氧化物酶和超氧化物歧化酶）活性上调以及肺中谷胱甘肽和核因子红细胞2相关因子2表达增强有关。柚皮苷和Nar - Dx - NCs发挥抗炎作用，表现为肿瘤坏死因子 - α和白细胞介素 - 1β的肺蛋白表达以及白细胞介素 - 6、干扰素 - γ、核因子 - κB和诱导型一氧化氮合酶的mRNA表达降低，同时白细胞介素 - 10表达增加。Nar - Dx - NCs的抗炎作用比柚皮苷更强。关于对细胞凋亡的影响，柚皮苷和Nar - Dx - NCs均显著降低Bcl - 2表达并增加Bax和P53表达。此外，柚皮苷或Nar - Dx - NCs可使增殖标志物Ki - 67的表达显著降低，且Nar - Dx - NCs的作用更明显。总之，Nar - Dx - NCs增强了柚皮苷对DEN/2AAF诱导的肺癌的预防作用，并通过抑制氧化应激和炎症以及改善凋亡信号的诱导和传播发挥抗癌作用。
