Everolimus-Induced Oral Mucositis Can be Prevented by Hippophae Rhamnoides Extract in Rats
Baran Akgunduz1, Muhammet Ozer2, Nazım Can Demircan3, Fatih Ozcicek3, Huseyin Salih Semiz4, Arzu Gezer5, Mehmet Aktas6, Ibrahim Cil7, Bahadir Suleyman81Department of Medical Oncology, Erzincan Binali Yildirim University, Erzincan, Turkey Department of Medical Oncology, Erzincan Binali Yildirim University, Erzincan, Turkey, 2Department of Internal Medicine, Capital Health Regional Medical Center, NJ, USA, 3Department of Medical Oncology, Marmara University Faculty of Medicine, İstanbul, Turkey, 4Department of Medical Oncology, Izmir Tepecik Research Hospital, İzmir, Turkey, 5Department of Embryology and Histology, Ataturk University Faculty of Medicine, Erzurum, Turkey, 6Department of Biochemistry, Erzincan Binali Yildirim University, Erzincan, Turkey, 7Department of Medical Oncology, Umraniye Research Hospital, Istanbul, Turkey, 8Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
Objectives: Oral mucositis is a significant toxicity related to the mammalian target of rapamycin inhibitor everolimus. Oxidative stress and pro-inflammatory cytokines, which contribute to treatment-related mucositis, can be targeted with Hippophae rhamnoides extract (HRE). Herein, we assessed the effects of HRE on everolimus-induced mucositis in rats. Methods: Eighteen rats were equally divided into healthy, everolimus, and everolimus plus HRE groups. Malondialdehyde (MDA) and total glutathione (tGSH) levels along with interleukin-1 beta (IL-1?) and tumor necrosis factor-alpha (TNF-?) gene expression levels were measured in the tongue and buccal mucosa tissues of all groups, histopathological changes were also evaluated. We tested the significance of variations with one-way variance analysis. We also analyzed the differences between groups with Kruskal–Wallis test and Mann–Whitney U-test. Results: HRE significantly decreased MDA and increased tGSH levels and reduced IL-1? and TNF-? gene expression in both tissues administered everolimus (p<0.001 for each). Histological examination revealed that HRE improved epithelial formation and keratinization, disrupted by everolimus, and alleviated everolimus-related mononuclear cell infiltration (p<0.05 for each). Conclusion: In light of these results, HRE may be a promising agent to manage oral mucositis caused by everolimus, given the lack of effective therapeutic options for this type of adverse event. Keywords: Everolimus, hippophae rhamnoides, oral mucositis
Cite This Article
Akgunduz B, Ozer M, Demircan N, Ozcicek F, Semiz H, Gezer A, Aktas M, Cil I, Suleyman B. Everolimus-Induced Oral Mucositis Can be Prevented by Hippophae Rhamnoides Extract in Rats. EJMI. 2021; 5(1): 81-88
Corresponding Author: Muhammet Ozer