Everolimus-Induced Oral Mucositis Can be Prevented by Hippophae Rhamnoides Extract in Rats

Eurasian Journal of Medical Investigation, vol.5, no.1, pp.81-88, 2021 (TRDizin)

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-1β) and tumor necrosis factor-alpha

(TNF-α) 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-1β and TNF-α 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