Naringin-Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation

Eman E Mohamed; Osama M Ahmed; Khairy M A Zoheir; Ahmed A G El-Shahawy; Shadi Tamur; Anwar Shams; Jack T Burcher; Anupam Bishayee; Adel Abdel-Moneim

doi:10.3390/cancers15205102

Naringin-Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation

Cancers (Basel). 2023 Oct 22;15(20):5102. doi: 10.3390/cancers15205102.

Authors

Affiliations

¹ Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt.
² Cell Biology Department, Biotechnology Research Institute, National Research Centre, Cairo 12622, Egypt.
³ Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62521, Egypt.
⁴ Departement of Pediatrics, College of Medicine, Taif University, Taif 21944, Saudi Arabia.
⁵ Departement of Pharmacology, College of Medicine, Taif University, Taif 21944, Saudi Arabia.
⁶ Centre of Biomedical Sciences Research, Deanship of Scientific Research, Taif University, Taif 21974, Saudi Arabia.
⁷ High Altitude Research Center, Taif University, Taif 21944, Saudi Arabia.
⁸ College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.

Abstract

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.

Keywords: acetylaminofluorene; anti-inflammatory; anticancer; antioxidant; apoptosis; diethylnitrosamine; lung cancer; naringin; naringin–dextrin nanocomposite.

Grants and funding

This research received no external funding.