Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation
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 diethylnitrosamin...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/20/5102 |
| _version_ | 1797574366003724288 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Eman E. Mohamed |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T21:21:58Z |
| format | Article |
| id | doaj.art-d02712f5080d443e93be38d2c77211fe |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:21:58Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d02712f5080d443e93be38d2c77211fe2023-11-19T16:00:36ZengMDPI AGCancers2072-66942023-10-011520510210.3390/cancers15205102Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell ProliferationEman E. Mohamed0Osama M. Ahmed1Khairy M. A. Zoheir2Ahmed A. G. El-Shahawy3Shadi Tamur4Anwar Shams5Jack T. Burcher6Anupam Bishayee7Adel Abdel-Moneim8Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef 62521, EgyptPhysiology Division, Faculty of Science, Beni-Suef University, Beni-Suef 62521, EgyptCell Biology Department, Biotechnology Research Institute, National Research Centre, Cairo 12622, EgyptMaterials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62521, EgyptDepartement of Pediatrics, College of Medicine, Taif University, Taif 21944, Saudi ArabiaDepartement of Pharmacology, College of Medicine, Taif University, Taif 21944, Saudi ArabiaCollege of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USACollege of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USAPhysiology Division, Faculty of Science, Beni-Suef University, Beni-Suef 62521, EgyptNanotechnology 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.https://www.mdpi.com/2072-6694/15/20/5102diethylnitrosamineacetylaminofluorenelung cancernaringinnaringin–dextrin nanocompositeanticancer |
| spellingShingle | 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 Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation Cancers diethylnitrosamine acetylaminofluorene lung cancer naringin naringin–dextrin nanocomposite anticancer |
| title | Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation |
| title_full | Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation |
| title_fullStr | Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation |
| title_full_unstemmed | Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation |
| title_short | Naringin–Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation |
| title_sort | naringin dextrin nanocomposite abates diethylnitrosamine acetylaminofluorene induced lung carcinogenesis by modulating oxidative stress inflammation apoptosis and cell proliferation |
| topic | diethylnitrosamine acetylaminofluorene lung cancer naringin naringin–dextrin nanocomposite anticancer |
| url | https://www.mdpi.com/2072-6694/15/20/5102 |
| work_keys_str_mv | AT emanemohamed naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT osamamahmed naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT khairymazoheir naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT ahmedagelshahawy naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT shaditamur naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT anwarshams naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT jacktburcher naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT anupambishayee naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation AT adelabdelmoneim naringindextrinnanocompositeabatesdiethylnitrosamineacetylaminofluoreneinducedlungcarcinogenesisbymodulatingoxidativestressinflammationapoptosisandcellproliferation |