Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways
<i>Background and Objectives:</i> Bleomycin-induced pulmonary fibrosis is one of the serious complications that may limit the use of bleomycin in cancer therapy. To date, there is no effective remedy for the amelioration of this condition. Donepezil, an anti-Alzheimer’s medication, has r...
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MDPI AG
2023-05-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/5/980 |
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| author | Shery Mina Dina M. Elfeky Ahmed M. Kabel Sabeha E. Hedya |
| author_facet | Shery Mina Dina M. Elfeky Ahmed M. Kabel Sabeha E. Hedya |
| author_sort | Shery Mina |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> Bleomycin-induced pulmonary fibrosis is one of the serious complications that may limit the use of bleomycin in cancer therapy. To date, there is no effective remedy for the amelioration of this condition. Donepezil, an anti-Alzheimer’s medication, has recently been proven to exhibit potent anti-inflammatory, antioxidant, and antifibrotic effects. To the best of our knowledge, this study represents the first study designed to investigate the prophylactic effects of donepezil, either alone or in combination with the classic anti-inflammatory drug prednisolone, in bleomycin-induced pulmonary fibrosis. <i>Methods:</i> This study was carried out on fifty rats, which were divided into five equal groups: control (Saline) group; bleomycin group; bleomycin + prednisolone group; bleomycin + donepezil group; and bleomycin + prednisolone + donepezil group. At the end of the experiments, bronchoalveolar lavage was performed to evaluate the total and differential leucocytic counts. The right lung was processed to assess the oxidative stress markers, proinflammatory cytokines, NLRP3 inflammasome, and transforming growth factor–beta1. The left lung was subjected to histopathological and immunohistochemical examination. <i>Results:</i> The administration of donepezil and/or prednisolone induced a significant amelioration of oxidative stress, inflammation, and fibrosis. In addition, these animals showed a significant amelioration of the histopathological changes of fibrosis, together with a significant decline in nuclear factor kappa B (p65) immunoexpression, compared to the group treated with bleomycin alone. However, the rats treated with the donepezil/prednisolone combination showed non-significant effects on the aforementioned parameters compared to the group treated with prednisolone alone. <i>Conclusions:</i> Donepezil may emerge as a promising drug that shows significant prophylactic effects against bleomycin-induced pulmonary fibrosis. |
| first_indexed | 2024-03-11T03:31:38Z |
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| language | English |
| last_indexed | 2024-03-11T03:31:38Z |
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| series | Medicina |
| spelling | doaj.art-c079241452624b2bb7b9fb3f8bec75c12023-11-18T02:23:11ZengMDPI AGMedicina1010-660X1648-91442023-05-0159598010.3390/medicina59050980Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic PathwaysShery Mina0Dina M. Elfeky1Ahmed M. Kabel2Sabeha E. Hedya3Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, EgyptDepartment of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, EgyptDepartment of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, EgyptDepartment of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt<i>Background and Objectives:</i> Bleomycin-induced pulmonary fibrosis is one of the serious complications that may limit the use of bleomycin in cancer therapy. To date, there is no effective remedy for the amelioration of this condition. Donepezil, an anti-Alzheimer’s medication, has recently been proven to exhibit potent anti-inflammatory, antioxidant, and antifibrotic effects. To the best of our knowledge, this study represents the first study designed to investigate the prophylactic effects of donepezil, either alone or in combination with the classic anti-inflammatory drug prednisolone, in bleomycin-induced pulmonary fibrosis. <i>Methods:</i> This study was carried out on fifty rats, which were divided into five equal groups: control (Saline) group; bleomycin group; bleomycin + prednisolone group; bleomycin + donepezil group; and bleomycin + prednisolone + donepezil group. At the end of the experiments, bronchoalveolar lavage was performed to evaluate the total and differential leucocytic counts. The right lung was processed to assess the oxidative stress markers, proinflammatory cytokines, NLRP3 inflammasome, and transforming growth factor–beta1. The left lung was subjected to histopathological and immunohistochemical examination. <i>Results:</i> The administration of donepezil and/or prednisolone induced a significant amelioration of oxidative stress, inflammation, and fibrosis. In addition, these animals showed a significant amelioration of the histopathological changes of fibrosis, together with a significant decline in nuclear factor kappa B (p65) immunoexpression, compared to the group treated with bleomycin alone. However, the rats treated with the donepezil/prednisolone combination showed non-significant effects on the aforementioned parameters compared to the group treated with prednisolone alone. <i>Conclusions:</i> Donepezil may emerge as a promising drug that shows significant prophylactic effects against bleomycin-induced pulmonary fibrosis.https://www.mdpi.com/1648-9144/59/5/980pulmonary fibrosisbleomycinprednisolonedonepezilrats |
| spellingShingle | Shery Mina Dina M. Elfeky Ahmed M. Kabel Sabeha E. Hedya Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways Medicina pulmonary fibrosis bleomycin prednisolone donepezil rats |
| title | Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways |
| title_full | Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways |
| title_fullStr | Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways |
| title_full_unstemmed | Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways |
| title_short | Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways |
| title_sort | ameliorative potential of donepezil with or without prednisolone in bleomycin induced pulmonary fibrosis in rats involvement of the anti inflammatory antioxidant and the antifibrotic pathways |
| topic | pulmonary fibrosis bleomycin prednisolone donepezil rats |
| url | https://www.mdpi.com/1648-9144/59/5/980 |
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